| altered peptide ligands trigger perforin- rather than fas-dependent cell lysis. | ctls lyse fas-expressing target cells by the concomitant action of a perforin- and a fas-dependent mechanism. this study analyzed whether target cells pulsed with t cell antagonists and other altered peptide ligands (apls) were susceptible selectively to only one of these two mechanisms. in vivo and in vitro activated t cells from transgenic mice expressing a tcr specific for lymphocytic choriomeningitis virus were used as effector cells. to distinguish between perforin- and fas-dependent cytoto ... | 1997 | 9379009 |
| nonmitogenic cd3 antibody reverses virally induced (rat insulin promoter-lymphocytic choriomeningitis virus) autoimmune diabetes without impeding viral clearance. | treatment with nonmitogenic cd3 ab reverses established autoimmune diabetes in nonobese diabetic mice by restoring self-tolerance, and is currently under clinical evaluation in patients presenting recent onset type i diabetes. due to the immunosuppressive potential of this strategy, it was relevant to explore how this treatment would influence the outcome of concomitant viral infections. in this study, we used a transgenic model of virally induced autoimmune diabetes (rat insulin promoter-lympho ... | 2002 | 11777992 |
| antibody prevents the establishment of persistent arenavirus infection in synergy with endogenous t cells. | a cardinal feature of the biology of lymphocytic choriomeningitis virus (lcmv) is its ability to establish persistent infections in mice. persistence is usually established by infection of the mouse during the in utero or neonatal period. susceptibility can be extended to the adult by treatment with immunosuppressive agents or by infection with immunosuppressive strains of lcmv. in this study we investigated the capacity of passively acquired anti-lcmv antibodies to prevent the establishment of ... | 1997 | 8985412 |
| interferon alpha/beta and interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo. | interferon (ifn)-alpha/beta and interleukin (il)-12 are cytokines critical in defense against viruses, but their cellular sources and mechanisms of regulation for in vivo expression remain poorly characterized. the studies presented here identified a novel subset of dendritic cells (dcs) as major producers of the cytokines during murine cytomegalovirus (mcmv) but not lymphocytic choriomeningitis virus (lcmv) infections. these dcs differed from those activated by toxoplasma antigen but were relat ... | 2002 | 11854364 |
| severe impairment of interleukin-1 and toll-like receptor signalling in mice lacking irak-4. | toll-like receptors (tlrs), which recognize pathogen-associated molecular patterns, and members of the pro-inflammatory interleukin-1 receptor (il-1r) family, share homologies in their cytoplasmic domains called toll/il-1r/plant r gene homology (tir) domains. intracellular signalling mechanisms mediated by tirs are similar, with myd88 (refs 5-8) and traf6 (refs 9, 10) having critical roles. signal transduction between myd88 and traf6 is known to involve the serine-threonine kinase il-1 receptor- ... | 2002 | 11923871 |
| immunological control of murine gammaherpesvirus infection is independent of perforin. | perforin-mediated cytotoxic t cell killing has been suggested to be of importance in the control of noncytopathic virus infections, based on studies with lymphocytic choriomeningitis virus (lcmv). we examined the role of perforin in a mouse model of gammaherpesvirus infection using transgenic perforin-deficient mice. previous work from this laboratory has shown that cd8 t cells are essential for the resolution of the acute lung infection and control of latently infected b cells in murine gamma-h ... | 1997 | 9267003 |
| serological evidence of murine pathogens in wild grey squirrels (sciurus carolinensis) in north wales. | wild grey squirrels in north wales were examined for their serological response to a range of laboratory mouse pathogens. nineteen squirrels were tested against 14 organisms and a high seroprevalence was found to several, including murine cytomegalovirus, mouse adenovirus, reovirus 3, rotavirus and sendai virus. four of the squirrels were seropositive for lymphocytic choriomeningitis virus, a zoonotic pathogen. none of the infections has previously been reported in squirrels. | 2002 | 12019534 |
| viruses and diabetes. | insulin-dependent diabetes mellitus (iddm) is a multifactorial disease. besides a genetic predisposition environmental factors have been implicated in the pathogenesis of beta cell destruction. among these environmental factors viruses have been the focus of many studies. some viruses are diabetogenic in animals, and others have been implicated as triggers in human iddm by temporal and geographical association between iddm and viral infections, serological evidence of infection in recently diagn ... | 2002 | 12021080 |
| virus-activated cd8 t cells and lymphokine-activated nk cells express the mast cell function-associated antigen, an inhibitory c-type lectin. | the mast cell function-associated ag (mafa) is an inhibitory c-type lectin that was originally identified on the cell surface of a rat mucosal mast cell line, rbl-2h3. we have cloned the mouse homologue of the rat mafa gene, and northern blot analysis revealed that mouse mafa (mmafa) gene expression was strongly induced in effector cd8 t cells and lymphokine-activated nk cells but not in effector cd4 t cells and in mouse mast cells. moreover, mmafa gene expression was only found in effector cd8 ... | 1998 | 9862665 |
| nk cell response to viral infections in beta 2-microglobulin-deficient mice. | because class i mhc ags have been implicated as modulators of target cell sensitivity to nk cell-mediated lysis, the regulation of virus infections and the fate of nk cells and their natural targets was examined in beta 2-microglobulin-deficient mice, which have defective class i mhc expression. infections with either the nk cell-sensitive murine cytomegalovirus (mcmv) or the nk cell-resistant lymphocytic choriomeningitis virus (lcmv) significantly augmented nk cell activity in either c57bl/6 (+ ... | 1995 | 7529286 |
| elevated generation of reactive oxygen/nitrogen species in hantavirus cardiopulmonary syndrome. | hantavirus cardiopulmonary syndrome (hcps) is a life-threatening respiratory disease characterized by profound pulmonary edema and myocardial depression. most cases of hcps in north america are caused by sin nombre virus (snv), which is carried asymptomatically by deer mice (peromyscus maniculatus). the underlying pathophysiology of hcps is poorly understood. we hypothesized that pathogenic snv infection results in increased generation of reactive oxygen/nitrogen species (rons), which contribute ... | 2002 | 12134039 |
| critical role for stat4 activation by type 1 interferons in the interferon-gamma response to viral infection. | interferons (ifns) are essential for host defense. although the antiviral effects of the type 1 ifns ifn-alpha and ifn-beta (ifn-alpha/beta) have been established, their immunoregulatory functions, especially their ability to regulate ifn-gamma production, are poorly understood. here we show that ifn-alpha/beta activate stat4 directly (stat, signal transducers and activators of transcription) and that this is required for ifn-gamma production during viral infections of mice, in concert with t ce ... | 2002 | 12242445 |
| homeostatic proliferation but not the generation of virus specific memory cd8 t cells is impaired in the absence of il-15 or il-15ralpha. | the generation and efficient maintenance of antigen specific memory t cells is essential for long-lasting immunological protection. antigen specific memory cd8 t cells are known to be maintained via antigen-independent homeostatic proliferation. however, signals that drive memory t cell generation and/or influence the slow turnover of memory t cells are unknown. recently, il-15 has received attention for its potential effect on memory cd8 t cells. in this report we examine the role of il-15 in t ... | 2002 | 12405201 |
| the differential contribution of granzyme a and granzyme b in cytotoxic t lymphocyte-mediated apoptosis is determined by the quality of target cells. | complementary approaches with purified molecules or transfected cytolytic effector cells have suggested that both, granzyme a (gzma) and granzyme b (gzmb), similarly contribute to ctl-mediatedand perforin (perf)-dependent apoptotic nuclear damage (dna fragmentation) in target cells. studies employing gzma or gzmb single-knockout mice on the other hand indicated that gzmb is the prominent ctl effector molecule for the rapid induction of dna fragmentation, with gzma playing only a minor part. we h ... | 2002 | 12115618 |
| new world arenavirus clade c, but not clade a and b viruses, utilizes alpha-dystroglycan as its major receptor. | alpha-dystroglycan (alpha-dg) has been identified as a major receptor for lymphocytic choriomeningitis virus (lcmv) and lassa virus, two old world arenaviruses. the situation with new world arenaviruses is less clear: previous studies demonstrated that oliveros virus also exhibited high-affinity binding to alpha-dg but that guanarito virus did not. to extend these initial studies, several additional old and new world arenaviruses were screened for entry into mouse embryonic stem cells possessing ... | 2002 | 11967329 |
| impaired anti-viral t cell responses due to expression of the ly49a inhibitory receptor. | inhibitory receptors specific for alleles of mhc class i proteins play an important role in determining the reactivity and specificity of nk cells. to determine whether these receptors are also able to regulate t cell functions, we have studied anti-viral immune responses in mice transgenic for a class i-specific inhibitory receptor, ly49a. although nontransgenic mice express ly49a primarily on nk cells and some t cells, the ly49a transgenic mice express ly49a on all lymphocytes, including t cel ... | 1999 | 10553080 |
| expression of hepatitis c virus proteins inhibits interferon alpha signaling in the liver of transgenic mice. | background & aims hepatitis c virus (hcv) is a major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma worldwide. the majority of patients treated with interferon alpha do not have a sustained response with clearance of the virus. the molecular mechanisms underlying interferon resistance are poorly understood. interferon-induced activation of the jak-stat (signal transducer and activator of transcription) signal transduction pathway is essential for the induction of an anti ... | 2003 | 12730885 |
| role of thymic output in regulating cd8 t-cell homeostasis during acute and chronic viral infection. | although it is well documented that cd8 t cells play a critical role in controlling chronic viral infections, the mechanisms underlying the regulation of cd8 t-cell responses are not well understood. using the mouse model of an acute and chronic lymphocytic choriomeningitis virus (lcmv) infection, we have examined the relative importance of peripheral t cells and thymic emigrants in the elicitation and maintenance of cd8 t-cell responses. virus-specific cd8 t-cell responses were compared between ... | 2005 | 16014905 |
| sensitizing antigen-specific cd8+ t cells for accelerated suicide causes immune incompetence. | death receptor-mediated activation-induced apoptosis of antigen-specific t cells is a major mechanism of peripheral tolerance induction and immune homeostasis. failure to undergo activation-induced cell death (aicd) is an important underlying cause of many autoimmune diseases. thus, enhancing the t cell's own suicide mechanism may provide an efficient therapy for the treatment of autoimmune diseases. bisindolylmaleimide viii (bis viii), a pkc inhibitor, can sensitize t cells for death receptor-i ... | 2003 | 12697738 |
| 4-1bb ligand induces cell division, sustains survival, and enhances effector function of cd4 and cd8 t cells with similar efficacy. | a costimulatory member of the tnfr family, 4-1bb, is expressed on activated t cells. although some reports have suggested that 4-1bb is primarily involved in cd8 t cell activation, in this report we demonstrate that both cd4 and cd8 t cells respond to 4-1bb ligand (4-1bbl) with similar efficacy. cd4 and cd8 tcr transgenic t cells up-regulate 4-1bb, ox40, and cd27 and respond to 4-1bbl-mediated costimulation during a primary response to peptide ag. 4-1bbl enhanced proliferation, cytokine producti ... | 2001 | 11466348 |
| increased expression of the nk cell receptor klrg1 by virus-specific cd8 t cells during persistent antigen stimulation. | the killer cell lectin-like receptor g1 (klrg1) is a natural killer cell receptor expressed by t cells that exhibit impaired proliferative capacity. here, we determined the klrg1 expression by virus-specific t cells. we found that repetitive and persistent antigen stimulation leads to an increase in klrg1 expression of virus-specific cd8+ t cells in mice and that virus-specific cd8+ t cells are mostly klrg1+ in chronic human viral infections (human immunodeficiency virus, cytomegalovirus, and ep ... | 2005 | 16140789 |
| in vivo selection of a lymphocytic choriomeningitis virus variant that affects recognition of the gp33-43 epitope by h-2db but not h-2kb. | cd8 t cells drive the protective immune response to lymphocytic choriomeningitis virus (lcmv) infection and are thus a determining force in the selection of viral variants. to examine how escape mutations affect the presentation and recognition of overlapping t-cell epitopes, we isolated an lcmv variant that is not recognized by t-cell receptor (tcr)-transgenic h-2db-restricted lcmv gp33-41-specific cytotoxic t lymphocytes (ctl). the variant virus carried a single-amino-acid substitution (valine ... | 2001 | 11333891 |
| [studies on the experimental pathogenicity of the lymphocytic choriomeningitis virus. iii. a directly visible inflammatory reaction in the mouse. viral edema of the hind leg]. | | 1963 | 13982379 |
| in vivo antiviral activity of 1,3-bis(2-chloroethyl)-1-nitrosourea. | a prolongation in the lives of swiss mice inoculated intracerebrally with lymphocytic choriomeningitis virus (lcm) was observed after treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (bcnu). a variety of treatment schedules, including therapy once or twice daily up to 17 days and single treatments at various times after virus inoculation, were employed. virus titers ranging to greater than 10(4) were detected in the blood and brains of surviving drug-treated animals. in three comparative stud ... | 1965 | 14339266 |
| sap is required for generating long-term humoral immunity. | long-lived plasma cells and memory b cells are the primary cellular components of long-term humoral immunity and as such are vitally important for the protection afforded by most vaccines. the sap gene has been identified as the genetic locus responsible for x-linked lymphoproliferative disease, a fatal immunodeficiency. mutations in sap have also been identified in some cases of severe common variable immunodeficiency disease. the underlying cellular basis of this genetic disorder remains uncle ... | 2003 | 12529646 |
| leflunomide-mediated suppression of antiviral antibody and tcell responses: differential restoration by uridine. | leflunomide is an isoxazol derivative with immunosuppressive capacities in various experimental allo- and xenotransplantation models. two main mechanisms of action have been described: inhibition of pyrimidine de novo synthesis and impairment of tyrosine phosphorylation of different tyrosine kinases involved in receptor signaling via b cell and cytokine receptors. | 2001 | 11544436 |
| diabetogenic potential of human pathogens uncovered in experimentally permissive beta-cells. | pancreatic beta-cell antiviral defense plays a critical role in protection from coxsackievirus b4 (cvb4)-induced diabetes. in the present study, we tested the hypothesis that interferon (ifn)-induced antiviral defense determines beta-cell survival after infection by the human pathogen cvb3, cytomegalovirus (cmv), and lymphocytic choriomeningitis virus (lcmv). we demonstrated that mice harboring beta-cells that do not respond to ifn because of the expression of the suppressor of cytokine signalin ... | 2003 | 12882919 |
| the role of stat1 in viral sensitization to lps. | the phenomenon of endotoxin sensitization by virus infection is well documented but not yet well understood. infection by virtually any viral agent will quickly induce expression of type i interferons (ifn-alpha/beta), and type ii ifn-gamma production will follow as nk cells and t cells are activated. it has been well established that type ii ifn pretreatment can intensify the effects of endotoxin. we have recently demonstrated that type i ifn induction by lymphocytic choriomeningitis virus (lcm ... | 2003 | 14577848 |
| specific history of heterologous virus infections determines anti-viral immunity and immunopathology in the lung. | having previously shown that previous immunity to one virus can influence the host response to a subsequent unrelated virus, we questioned whether the outcome to a given virus infection would be altered in similar or different ways by previous immunity to different viruses, and whether immunity to a given virus would have similar effects on all subsequent infections. in mouse models of respiratory viral infections, immunity to lymphocytic choriomeningitis virus (lcmv), murine cytomegalovirus (mc ... | 2003 | 14507643 |
| pathogens of house mice on arid boullanger island and subantarctic macquarie island, australia. | studies on island populations of house mice (mus domesticus) and their viruses reveal insights into viral persistence in isolated communities. we surveyed the ectoparasites, endoparasites, and antiviral antibodies for 11 murine viruses and two bacteria of house mice inhabiting two islands off australia. house mice on boullanger island were seropositive to two viruses, murine cytomegalovirus and epizootic diarrhea of infant mice. on subantarctic macquarie island, house mice were seropositive for ... | 2003 | 14733270 |
| very diverse cd8 t cell clonotypic responses after virus infections. | we measured cd8 t cell clonotypic diversity to three epitopes recognized in c57bl/6 mice infected with mouse hepatitis virus, strain jhm, or lymphocytic choriomeningitis virus. we isolated epitope-specific t cells with an ifn-gamma capture assay or mhc class i/peptide tetramers and identified different clonotypes by vbeta chain sequence analysis. in agreement with our previous results, the number of different clonotypes responding to all three epitopes fit a log-series distribution. from these d ... | 2004 | 14978121 |
| role of toll-like receptors in costimulating cytotoxic t cell responses. | stimulation of toll-like receptors (tlr) by pathogen-derived compounds leads to activation of apc, facilitating the induction of protective immunity. this phenomenon is the basis of most adjuvant formulations currently in development. here, we tested the ability of tlr2, 3, 4, 5, 7 and 9 signaling to enhance ctl responses upon vaccination with virus-like particles. stimulation of tlr2 and 4 failed to increase ctl responses, whereas ligands for tlr3, 5 and 7 exhibited moderate adjuvant function. ... | 2003 | 12778463 |
| a role for the granzyme b inhibitor serine protease inhibitor 6 in cd8+ memory cell homeostasis. | generation and maintenance of protective immunological memory is the goal of vaccination programs. it has recently become clear that cd8+ memory t cells are derived directly from ctls. the mechanisms underlying this transformation and the subsequent survival of memory cells are not completely understood. however, some effector molecules required by ctls to eliminate infected cells have also been shown to control the number of ag-specific cells. we report that memory cells express high levels of ... | 2004 | 15356127 |
| cd8 t cell responses to lymphocytic choriomeningitis virus in early growth response gene 1-deficient mice. | previous in vitro work has implicated a role for transcriptional factor early growth response gene 1 (egr1) in regulating immune responses. however, the in vivo role of egr1 in orchestrating t cell responses has not been studied. to investigate the importance of egr1 in t cell immunity, we compared ag-specific cd8 t cell responses between wild type (+/+) and egr1-deficient (egr1-/-) mice following an acute infection with lymphocytic choriomeningitis virus (lcmv). these studies revealed that the ... | 2004 | 15356133 |
| antigen-independent memory cd8 t cells do not develop during chronic viral infection. | memory t cells can persist for extended periods in the absence of antigen, and long-term t cell immunity is often seen after acute infections. paradoxically, there have been observations suggesting that t cell memory may be antigen-dependent during chronic infections. to elucidate the underlying mechanisms we have compared memory cd8 t cell differentiation during an acute versus chronic infection by using the mouse model of infection with lymphocytic choriomeningitis virus. we found that during ... | 2004 | 15505208 |
| among cxcr3 chemokines, ifn-gamma-inducible protein of 10 kda (cxc chemokine ligand (cxcl) 10) but not monokine induced by ifn-gamma (cxcl9) imprints a pattern for the subsequent development of autoimmune disease. | infection of the pancreas with lymphocytic choriomeningitis virus results in rapid and differential expression among cxcr3 chemokines. ifn-gamma-inducible protein of 10 kda (ip-10), in contrast with monokine induced by ifn-gamma and ifn-inducible t cell-alpha chemoattractant, is strongly expressed within 24 h postinfection. blocking of ip-10, but not monokine induced by ifn-gamma, aborts severity of ag-specific injury of pancreatic beta cells and abrogates type 1 diabetes. mechanistically, ip-10 ... | 2003 | 14662890 |
| increased epitope-specific cd8+ t cells prevent murine coronavirus spread to the spinal cord and subsequent demyelination. | cd8+ t cells are important for clearance of neurotropic mouse hepatitis virus (mhv) strain a59, although their possible role in a59-induced demyelination is not well understood. we developed an adoptive-transfer model to more clearly elucidate the role of virus-specific cd8+ t cells during the acute and chronic phases of infection with a59 that is described as follows. c57bl/6 mice were infected with a recombinant a59 virus expressing the gp33 epitope, an h-2db-restricted cd8+ t-cell epitope enc ... | 2005 | 15731231 |
| defective b cell responses in the absence of sh2d1a. | more than half of patients with x-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein sh2d1a, suffer from an extreme susceptibility to epstein-barr virus. one-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. here we show that in sh2d1a(-/-) mice, both primary and secondary responses of all ig subclasses are severely impaired in response to specific antigens. because germinal centers were a ... | 2005 | 15774582 |
| limited in vivo reactivity of polyclonal effector cytotoxic t cells towards altered peptide ligands. | t cell responses are regulated by the affinity/avidity of the t cell receptor for the mhc/peptide complex, available costimulation and duration of antigenic stimulation. altered peptide ligands (apls) are usually recognized with a reduced affinity/avidity by the t cell receptor and are often able to only partially activate t cells in vitro or may even function as antagonists. here we assessed the ability of apls derived from peptide p33 of lymphocytic choriomeningitis virus (lcmv) to mediate lys ... | 2005 | 15857805 |
| constitutive expression of ccr7 directs effector cd8 t cells into the splenic white pulp and impairs functional activity. | antigenic stimulation down-regulates ccr7 on effector t cells. to analyze the importance of ccr7 down-regulation, transgenic (tg) mice constitutively expressing ccr7 were generated. cd8 t cells with defined ag specificity were obtained by breeding ccr7-tg mice with p14 tcr-tg mice specific for lymphocytic choriomeningitis virus. transgenic ccr7 expression did not impair proliferation of p14.ccr7 t cells induced by lymphocytic choriomeningitis virus infection, but prevented ccr7 down-regulation. ... | 2004 | 15322160 |
| selective loss of natural killer t cells by apoptosis following infection with lymphocytic choriomeningitis virus. | natural killer t (nkt) cells, a unique subpopulation of t cells, coexpress markers also present on nk cells and recognize the major histocompatibility complex class i-like cd1d1 molecule. we studied the effect of an acute virus infection on nkt cells. mice were infected with the nonhepatotropic armstrong strain of lymphocytic choriomeningitis virus (lcmv), and at various times postinfection, mononuclear cells from the liver, peritoneum, and spleen were isolated. it was found that within 2 to 3 d ... | 2001 | 11602716 |
| differential regulation of interferon regulatory factor (irf)-7 and irf-9 gene expression in the central nervous system during viral infection. | interferon regulatory factors (irfs) are a family of transcription factors involved in the regulation of the interferons (ifns) and other genes that may have an essential role in antiviral defense in the central nervous system, although this is currently not well defined. therefore, we examined the regulation of irf gene expression in the brain during viral infection. several irf genes (irf-2, -3, -5, -7, and -9) were expressed at low levels in the brain of uninfected mice. following intracrania ... | 2005 | 15919906 |
| opposing effects of cxcr3 and ccr5 deficiency on cd8+ t cell-mediated inflammation in the central nervous system of virus-infected mice. | t cells play a key role in the control of viral infection in the cns but may also contribute to immune-mediated cell damage. to study the redundancy of the chemokine receptors cxcr3 and ccr5 in regulating virus-induced cd8+ t cell-mediated inflammation in the brain, cxcr3/ccr5 double-deficient mice were generated and infected intracerebrally with noncytolytic lymphocytic choriomeningitis virus. because these chemokine receptors are mostly expressed by overlapping subsets of activated cd8+ t cell ... | 2005 | 16034118 |
| virus-induced polyclonal b cell activation improves protective ctl memory via retained cd27 expression on memory ctl. | different viruses elicit distinct phenotypes of memory cytotoxic t lymphocytes (ctl). this is reflected in differential expression of homing receptors and costimulatory molecules like cd27. memory ctl retained cd27 following lymphocytic choriomeningitis virus (lcmv) infection, but not after immunization with recombinant vaccinia virus or tumor cells expressing lcmv glycoprotein. stable cd27 expression on memory ctl required ligation by cd70 expressed on polyclonally activated b cells during the ... | 2005 | 16231287 |
| a role for dual viral hits in causation of subacute sclerosing panencephalitis. | subacute sclerosing panencephalitis (sspe) is a progressive fatal neurodegenerative disease associated with persistent infection of the central nervous system (cns) by measles virus (mv), biased hypermutations of the viral genome affecting primarily the matrix (m) gene with the conversion of u to c and a to g bases, high titers of antibodies to mv, and infiltration of b cells and t cells into the cns. neither the precipitating event nor biology underlying the mv infection is understood, nor is t ... | 2005 | 16260490 |
| ly9 (cd229)-deficient mice exhibit t cell defects yet do not share several phenotypic characteristics associated with slam- and sap-deficient mice. | signaling lymphocyte activation molecule (slam) family receptors are critically involved in modulating innate and adaptive immune responses. several slam family receptors have been shown to interact with the adaptor molecule sap; however, subsequent intracellular signaling is poorly defined. notably, mutations in slam-associated protein (sap) lead to x-linked lymphoproliferative disease, a rare but fatal immunodeficiency. although the slam family member ly9 (cd229) is known to interact with sap, ... | 2006 | 16365421 |
| cutting edge: mhc class ii-restricted killing in vivo during viral infection. | class ii-restricted cd4 t cell-mediated killing of target cells has previously been documented in vitro but not in vivo. in this study, we demonstrate cd4-dependent mhc class ii-restricted killing in lymphocytic choriomeningitis virus-infected mice in vivo using an in vivo cytotoxicity assay that features class ii-expressing b cells as targets. | 2005 | 15634878 |
| immunoproteasome-deficient mice mount largely normal cd8+ t cell responses to lymphocytic choriomeningitis virus infection and dna vaccination. | during viral infection, constitutive proteasomes are largely replaced by immunoproteasomes, which display distinct cleavage specificities, resulting in different populations of potential cd8(+) t cell epitope peptides. immunoproteasomes are believed to be important for the generation of many viral cd8(+) t cell epitopes and have been implicated in shaping the immunodominance hierarchies of cd8(+) t cell responses to influenza virus infection. however, it remains unclear whether these conclusions ... | 2005 | 16002717 |
| antiviral immune responses in gene-targeted mice expressing the immunoglobulin heavy chain of virus-neutralizing antibodies. | two gene-targeted immunoglobulin heavy chain transgenic mouse strains, tgh(kl25) and tgh(vi10), expressing neutralizing specificities for lymphocytic choriomeningitis virus and vesicular stomatitis virus, respectively, have been generated. three days after lymphocytic choriomeningitis virus infection, tgh(kl25) mice showed a thymus-independent neutralizing igm response followed by thymus-dependent (td) igg. in contrast, wt mice mounted only a td igg response around day 80. these observations ind ... | 2003 | 14569006 |
| expression, refolding and crystallization of murine mhc class i h-2db in complex with human beta2-microglobulin. | beta2-microglobulin (beta2m) is non-covalently linked to the major histocompatibility (mhc) class i heavy chain and interacts with cd8 and ly49 receptors. murine mhc class i can bind human beta2m (hbeta2m) and such hybrid molecules are often used in structural and functional studies. the replacement of mouse beta2m (mbeta2m) by hbeta2m has important functional consequences for mhc class i complex stability and specificity, but the structural basis for this is unknown. to investigate the impact o ... | 2005 | 16511243 |
| responses of the peyer's patches in germ-free mice to antigenic stimulation. | lymph nodes, spleens, and peyer's patches of germ-free mice are relatively inactive. the tissues are small and contain rare, small, indistinct, germinal zones. when exposed to antigenic stimuli (salmonella paratyphi a and lymphocytic choriomeningitis virus), the tissues become larger and germinal zones appear coincident with antibodies in the blood. the peyer's patches were activated if antigen was absorbed from the intestinal lumen into the circulation but not if the antigen was administered pa ... | 1970 | 16557807 |
| activation of tyk2 and stat3 is required for the apoptotic actions of interferon-beta in primary pro-b cells. | the growth-inhibitory effects of type 1 interferons (ifns) (ifnalpha/beta) are complex, and the role of apoptosis in their antigrowth effects is variable and not well understood. we have examined primary murine interleukin-7-dependent bone marrow-derived pro-b cells, where ifnbeta, but not ifnalpha, induces programmed cell death (pcd). ifnbeta-stimulated apoptosis is the same in pro-b cells derived from wild type and stat1(-/-) mice. however, in pro-b cells from tyk2(-/-) mice, where there is no ... | 2006 | 16601124 |
| reviving exhausted t lymphocytes during chronic virus infection by b7-h1 blockade. | cytotoxic t lymphocytes (ctls) are killer cells that are crucial in the control of viral pathogens and cancers. they can become exhausted during chronic viral infection, a phenomenon that consists of a reduction in both number and functionality of ctls. recently, barber and colleagues demonstrated that b7-h1 (also called pd-l1), a cell-surface molecule that is widely distributed in tissues, was necessary for the maintenance of t-cell exhaustion in a chronic-infection mouse model of lymphocytic c ... | 2006 | 16650803 |
| isg15, an interferon-stimulated ubiquitin-like protein, is not essential for stat1 signaling and responses against vesicular stomatitis and lymphocytic choriomeningitis virus. | isg15 is an interferon-induced ubiquitin-like modifier which can be conjugated to distinct, but largely unknown, proteins. isg15 has been implicated in a variety of biological activities, which encompass antiviral defense, immune responses, and pregnancy. mice lacking ubp43 (usp18), the isg15-deconjugating enzyme, develop a severe phenotype with brain injuries and lethal hypersensitivity to poly(i:c). it has been reported that an augmented conjugation of isg15 in the absence of ubp43 induces pro ... | 2005 | 16024773 |
| an altered t cell repertoire in mecl-1-deficient mice. | immunoproteasome subunits low-molecular mass polypeptide (lmp)2 and lmp7 affect ag presentation by mhc class i molecules. in the present study, we investigated the function of the third immunosubunit lmp10/multicatalytic endopeptidase complex-like (mecl)-1 (beta2i) in mecl-1 gene-targeted mice. the number of cd8+ splenocytes in mecl-1-/- mice was 20% lower than in wild-type mice. infection with lymphocytic choriomeningitis virus (lcmv) elicited a markedly reduced cytotoxic t cell (ctl) response ... | 2006 | 16709825 |
| trail deficiency delays, but does not prevent, erosion in the quality of "helpless" memory cd8 t cells. | in this study, we investigated the role of trail in ag-specific cd8 t cell homeostasis after viral infection. trail deficiency does not influence the kinetics of the ag-specific cd8 t cell responses, and cd8 t cells in trail-deficient mice were able to expand, contract, and generate functional memory cell numbers that were indistinguishable from trail-sufficient wild-type cd8 t cells after acute lymphocytic choriomeningitis virus infection. interestingly, the ability of "helpless" cd8 t cells to ... | 2006 | 16818756 |
| expression of lymphotoxin beta governs immunity at two distinct levels. | interaction of lymphotoxin alpha(1)beta(2) (ltalpha(1)beta(2)) with its receptor is key for the generation and maintenance of secondary lymphoid organ microstructure. we used mice conditionally deficient for ltbeta on different lymphocyte subsets to determine how the ltbeta-dependent lymphoid structure influences immune reactivity. all conditionally ltbeta-deficient mice mounted normal immune responses against vesicular stomatitis virus (vsv), and were protected against lymphocytic choriomeningi ... | 2006 | 16841297 |
| transgenic expression of the viral flip mc159 causes lpr/gld-like lymphoproliferation and autoimmunity. | death receptor-induced programmed cell death (pcd) is crucial for the maintenance of immune homeostasis. however, interference of downstream death receptor signaling by genetic ablation or transgenic (tg) expression of different apoptosis inhibitors often impairs lymphocyte activation. the viral flice (caspase-8)-like inhibitor proteins (v-flips) are potent inhibitors of death receptor-induced apoptosis and programmed necrosis. we generated tg mice expressing the v-flip mc159 from molluscum cont ... | 2006 | 16951343 |
| hiv: tired t cells turn around. | | 2006 | 16988698 |
| coordinated regulation and widespread cellular expression of interferon-stimulated genes (isg) isg-49, isg-54, and isg-56 in the central nervous system after infection with distinct viruses. | the interferon (ifn)-stimulated genes (isgs) isg-49, isg-54, and isg-56 are highly responsive to viral infection, yet the regulation and function of these genes in vivo are unknown. we examined the simultaneous regulation of these isgs in the brains of mice during infection with either lymphocytic choriomeningitis virus (lcmv) or west nile virus (wnv). expression of the isg-49 and isg-56 genes increased significantly during lcmv infection, being widespread and localized predominantly to common a ... | 2007 | 17079283 |
| heat shock up-regulates lmp2 and lmp7 and enhances presentation of immunoproteasome-dependent epitopes. | the heat shock response is a canonical regulatory pathway by which cellular stressors such as heat and oxidative stress alter the expression of stress-responsive genes. some of these stress-responsive genes (heat shock proteins and mhc class i (mhc i)-related chains) play a significant role in the immune system. in this study, we have investigated the impact of stimulating the heat shock response on genes involved in the mhc i presentation pathway. we report that two inducible subunits of the pr ... | 2006 | 17142736 |
| chronic antigen stimulation alone is sufficient to drive cd8+ t cell exhaustion. | the failure of cd8(+) t cells to respond to chronic infection has been termed "exhaustion" and describes the condition in which cd8(+) t cells exhibit reduced differentiation, proliferation, and effector function. cd8(+) t cell exhaustion has been extensively studied in the murine model of chronic infection, lymphocytic choriomeningitis virus (lcmv). although lcmv-based studies have yielded many interesting findings, they have not allowed for discrimination between the roles of cytokine- and ag- ... | 2009 | 19454664 |
| the role of endoplasmic reticulum-associated aminopeptidase 1 in immunity to infection and in cross-presentation. | endoplasmic reticulum-associated aminopeptidase 1 (erap1) is involved in the final processing of endogenous peptides presented by mhc class i molecules to ctls. we generated erap1-deficient mice and analyzed cytotoxic responses upon infection with three viruses, including lymphocytic choriomeningitis virus, which causes vigorous t cell activation and is controlled by ctls. despite pronounced effects on the presentation of selected epitopes, the in vivo cytotoxic response was altered for only one ... | 2007 | 17277129 |
| hantavirus and arenavirus antibody prevalence in rodents and humans in trentino, northern italy. | the spatial and temporal distribution of hantavirus and arenavirus antibody-positive wild rodents in trentino, italy, was studied using immunofluorescence assays (ifa) in two long-term sites trapped in 2000-2003, and six other sites trapped in 2002. the overall hantavirus seroprevalence in the bank voles, clethrionomys glareolus (n=229) screened for puumala virus (puuv) antibodies was 0.4%, and that for apodemus flavicollis mice (n=1416) screened for dobrava virus (dobv) antibodies was 0.2%. ant ... | 2006 | 16371172 |
| arenaviruses. | the arenaviridae family contains 22 recognized virus species, each of them strongly associated with a rodent species (except tacaribe virus which is associated with a species of bat), suggesting an ancient co-evolutionary process. although the concept of co-evolution between rodents and arenaviruses is now largely accepted, little has been uncovered in terms of dating the phenomenon and the mechanisms of evolution, including speciation and pathogenicity. these questions are targeted in the prese ... | 2007 | 17848068 |
| generation and maintenance of listeria-specific cd8+ t cell responses in perforin-deficient mice chronically infected with lcmv. | disruption of the perforin gene results in primary immunodeficiency and an increased susceptibility to opportunistic pathogens. perforin-deficient (pko) mice fail to clear primary lymphocytic choriomeningitis virus (lcmv) armstrong, resulting in persistent infection and functional exhaustion of virus-specific cd8+ t cells. cd8+ t cell responses to listeria monocytogenes (lm) challenge within the first week after lcmv infection were diminished in both wt and pko mice, and correlated with enhanced ... | 2008 | 17936870 |
| ube1l and protein isgylation are not essential for alpha/beta interferon signaling. | the expression of ubiquitin-like modifier isg15 and its conjugation to target proteins are highly induced by interferon (ifn) stimulation and during viral and bacterial infections. however, the biological significance of this modification has not been clearly understood. to investigate the function of protein modification by isg15, we generated a mouse model deficient in ube1l, an isg15-activating enzyme. ube1l-/- mice did not produce isg15 conjugates but expressed free isg15 normally. isgylatio ... | 2006 | 16382139 |
| perforin-deficient cd8+ t cells mediate fatal lymphocytic choriomeningitis despite impaired cytokine production. | intracerebral (i.c.) infection with lymphocytic choriomeningitis virus (lcmv) is one of the most studied models for virus-induced immunopathology, and based on results from perforin-deficient mice, it is currently assumed that fatal disease directly reflects perforin-mediated cell lysis. however, recent studies have revealed additional functional defects within the effector t cells of lcmv-infected perforin-deficient mice, raising the possibility that perforin may not be directly involved in med ... | 2006 | 16414999 |
| card6 is interferon inducible but not involved in nucleotide-binding oligomerization domain protein signaling leading to nf-kappab activation. | we have previously reported the cloning and characterization of card6, a caspase recruitment domain (card)-containing protein that is structurally related to the interferon (ifn)-inducible gtpases. card6 associates with microtubules and with receptor-interacting protein 2 (rip2). rip2 mediates nf-kappab activation induced by the intracellular nucleotide-binding oligomerization domain (nod) receptors that sense bacterial peptidoglycan. here we report that the expression of card6 and rip2 in bone ... | 2008 | 18160713 |
| irak-4 kinase activity is required for irak-4-dependent innate and adaptive immune responses. | interleukin-1 receptor-associated kinase (irak)-4 is a serine-threonine kinase that plays an important role in innate and adaptive immune responses. while the requirement of irak-4 kinase activity has been studied in the context of il-1r signaling, it is not clear whether irak-4 requires its kinase function for all of its roles in the immune system. irak-4 kinase-dead knock-in (irak-4kd/kd) mice were generated to further elucidate whether irak-4 kinase activity is required for irak-4 to induce c ... | 2008 | 18286567 |
| enhancing therapeutic vaccination by blocking pd-1-mediated inhibitory signals during chronic infection. | therapeutic vaccination is a potentially promising strategy to enhance t cell immunity and viral control in chronically infected individuals. however, therapeutic vaccination approaches have fallen short of expectations, and effective boosting of antiviral t cell responses has not always been observed. one of the principal reasons for the limited success of therapeutic vaccination is that virus-specific t cells become functionally exhausted during chronic infections. we now provide a novel strat ... | 2008 | 18332181 |
| do thymically and strictly extrathymically developing t cells generate similar immune responses? | if present in sufficient numbers, could extrathymic t cells substitute for thymus-derived t cells? to address this issue, we studied extrathymic t cells that develop in athymic mice under the influence of oncostatin m (om). in this model, extensive t-cell development is probably due to amplification of a minor pathway of t-cell differentiation taking place only in the lymph nodes. extrathymic cd4 t cells expanded poorly and were deficient in providing b-cell help after infection with vesicular s ... | 2004 | 15070691 |
| overexpression of lymphotoxin in t cells induces fulminant thymic involution. | activated lymphocytes and lymphoid-tissue inducer cells express lymphotoxins (lts), which are essential for the organogenesis and maintenance of lymphoreticular microenvironments. here we describe that t-cell-restricted overexpression of lt induces fulminant thymic involution. this phenotype was prevented by ablation of the lt receptors tumor necrosis factor receptor (tnfr) 1 or lt beta receptor (ltbetar), representing two non-redundant pathways. multiple lines of transgenic ltalphabeta and ltal ... | 2008 | 18483211 |
| evaluating antigen-specific cytotoxic t lymphocyte responses by a novel mouse granzyme b elispot assay. | we have established novel elisa- and elispot-based assays specific for the detection of a potent cytotoxic mediator, granzyme b (grb), for the assessment of antigen-specific cytotoxic t lymphocyte responses in mice. the sensitivity and specificity of our assays was demonstrated by elisa using purified mouse grb and supernatants and cell lysates of cytotoxic lymphocytes derived from grb-deficient mice. no reactivity was observed by the grb elisa in grb-deficient cells. the mouse grb elispot was s ... | 2006 | 16375915 |
| myd88 plays a critical t cell-intrinsic role in supporting cd8 t cell expansion during acute lymphocytic choriomeningitis virus infection. | during acute lymphocytic choriomeningitis virus (lcmv) infection, cd8 t cells rapidly expand and differentiate into effectors that are required for viral clearance. the accumulation of activated t cells is greatly reduced in mice lacking the adaptor molecule myd88. although myd88 has generally been considered to indirectly regulate adaptive immune responses by controlling inflammatory cytokine production and ag presentation in innate immune cells, in this study, we identify an unappreciated cell ... | 2008 | 18768833 |
| immunopathological basis of lymphocytic choriomeningitis virus-induced chorioretinitis and keratitis. | the infection of humans with the rodent-borne lymphocytic choriomeningitis virus (lcmv) can lead to central nervous system disease in adults or severe neurological disease with hydrocephalus and chorioretinitis in children infected congenitally. although lcmv-induced meningitis and encephalitis have been studied extensively, the immunopathological mechanisms underlying lcmv infection-associated ocular disease remain elusive. we report here that the intraocular administration of the neurotropic l ... | 2009 | 18945766 |
| memory cd8 t-cell compartment grows in size with immunological experience. | memory cd8 t cells, generated by natural pathogen exposure or intentional vaccination, protect the host against specific viral infections. it has long been proposed that the number of memory cd8 t cells in the host is inflexible, and that individual cells are constantly competing for limited space. consequently, vaccines that introduce over-abundant quantities of memory cd8 t cells specific for an agent of interest could have catastrophic consequences for the host by displacing memory cd8 t cell ... | 2009 | 19005468 |
| effective t-cell immune responses in the absence of the serine/threonine kinase rip2. | the serine/threonine kinase rip2 has been reported to be essential for nod1 and nod2 mediated cell activation, and has been suggested to play a role in the signaling cascade downstream of the t-cell receptor. we sought to ascertain the exact role of rip2 in t-helper cell differentiation and cd8+ t-cell effector function in vivo and in vitro. in contrast to previous reports, we found that rip2-deficient t cells did not exhibit impaired proliferation upon tcr engagement in vitro, and differentiati ... | 2008 | 18403232 |
| brief report: lymphocytic choriomeningitis virus transmitted through solid organ transplantation--massachusetts, 2008. | lymphocytic choriomeningitis virus (lcmv) is a rodent-borne arenavirus found worldwide. house mice (mus musculus) are the natural reservoir, but lcmv also can infect other wild, pet, and laboratory rodents (e.g., rats, mice, guinea pigs, and hamsters). humans can be infected through exposure to rodent excreta. person-to-person transmission has occurred only through maternal-fetal transmission and solid organ transplantation. lcmv infection in humans can be asymptomatic or cause a spectrum of ill ... | 2008 | 18650788 |
| immunoregulatory mechanisms triggered by viral infections protect from type 1 diabetes in mice. | type 1 diabetes (t1d) is an autoimmune disease that is caused by the destruction of insulin-producing beta cells. viral infections induce immune responses that can damage beta cells and promote t1d or on the other hand prevent the development of the disease. however, the opposing roles of viral infections in t1d are not understood mechanistically. we report here that viruses that do not inflict damage on beta cells provided protection from t1d by triggering immunoregulatory mechanisms. infection ... | 2009 | 19478458 |
| effector t-cell differentiation during viral and bacterial infections: role of direct il-12 signals for cell fate decision of cd8(+) t cells. | to study the role of il-12 as a third signal for t-cell activation and differentiation in vivo, direct il-12 signaling to cd8(+) t cells was analyzed in bacterial and viral infections using the p14 t-cell adoptive transfer model with cd8(+) t cells that lack the il-12 receptor. results indicate that cd8(+) t cells deficient in il-12 signaling were impaired in clonal expansion after listeria monocytogenes infection but not after infection with lymphocytic choriomeningitis virus, vaccinia virus or ... | 2009 | 19548244 |
| lymphocytic choriomeningitis infection undetected by dirty-bedding sentinel monitoring and revealed after embryo transfer of an inbred strain derived from wild mice. | persistent lcmv infection in wild-derived mai/pas mice housed under conventional conditions remained undetected for a decade, despite periodic health monitoring using dirty-bedding sentinels. when mai/pas mice were rederived by embryo transfer, recipient mothers produced antilcmv antibodies, which first revealed the presence of the virus in the colony. before this information was obtained, mai/pas mice had been shipped to another facility, undergone cesarean rederivation there, and been introduc ... | 2007 | 17605342 |
| bcl6 and blimp-1 are reciprocal and antagonistic regulators of t follicular helper cell differentiation. | effective b cell-mediated immunity and antibody responses often require help from cd4+ t cells. it is thought that a distinct cd4+ effector t cell subset, called t follicular helper cells (t(fh)), provides this help; however, the molecular requirements for t(fh) differentiation are unknown. we found that expression of the transcription factor bcl6 in cd4+ t cells is both necessary and sufficient for in vivo t(fh) differentiation and t cell help to b cells in mice. in contrast, the transcription ... | 2009 | 19608860 |
| regulation of homeostatic chemokine expression and cell trafficking during immune responses. | the chemokines ccl21 and cxcl13 are immune factors that dictate homing and motility of lymphocytes and dendritic cells in lymphoid tissues. however, the means by which these chemokines are regulated and how they influence cell trafficking during immune responses remain unclear. we show that ccl21 and cxcl13 are transiently down-regulated within lymphoid tissues during immune responses by a mechanism controlled by the cytokine interferon-gamma. this modulation was found to alter the localization ... | 2007 | 17673664 |
| the hepatitis c virus non-structural ns5a protein impairs both the innate and adaptive hepatic immune response in vivo. | the role of hepatitis c virus (hcv) protein non-structural (ns) 5a in hcv-associated pathogenesis is still enigmatic. to investigate the in vivo role of ns5a for viral persistence and virus-associated pathogenesis a transgenic (tg) mouse model was established. mice with liver-targeted ns5a transgene expression were generated using the albumin promoter. alterations in the hepatic immune response were determined by western blot, infection by lymphocytic choriomeningitis virus (lcmv), and using tra ... | 2009 | 19674968 |
| cbl-b regulates antigen-induced tcr down-regulation and ifn-gamma production by effector cd8 t cells without affecting functional avidity. | the e3 ubiquitin ligase cbl-b is a negative regulator of tcr signaling that: 1) sets the activation threshold for t cells; 2) is induced in anergic t cells; and 3) protects against autoimmunity. however, the role of cbl-b in regulating cd8 t cell activation and functions during physiological t cell responses has not been systematically examined. using the lymphocytic choriomeningitis virus infection model, we show that cbl-b deficiency did not significantly affect the clonal expansion of virus-s ... | 2007 | 18025165 |
| mice deficient in stem cell antigen-1 (sca1, ly-6a/e) develop normal primary and memory cd4+ and cd8+ t-cell responses to virus infection. | stem cell antigen-1 (sca1, ly-6a/e) is a well-established marker of murine hematopoietic stem cells, and also is expressed on memory t cells. it has been suggested that the functional maintenance of t-cell memory requires the expression of sca1 on a specialized population of memory t cells termed "memory stem cells". here, we evaluate the requirement for sca1 in the primary t-cell response to virus infection, and in the establishment and maintenance of t-cell memory. we find that sca1 expression ... | 2009 | 19384870 |
| rip2 contributes to nod signaling but is not essential for t cell proliferation, t helper differentiation or tlr responses. | receptor-interacting protein 2 (rip2), also known as cardiak and rick, has been reported to play a role in both adaptive t cell responses and innate immunity as a mediator in tlr signaling and nucleotide-binding oligomerization domain (nod) signaling. because initial reports remain controversial, we have further examined both innate and adaptive immune responses in rip2-deficient mice on the c57bl/6 background. despite the up-regulation of rip2 after t cell activation, we could not detect any de ... | 2008 | 18085666 |
| differential microenvironment localization of effector and memory cd8 t cells. | cd8 t cells are critical for the clearance of intracellular pathogens. upon infection, naive cd8 t cells differentiate into effector cells that target and eliminate infected cells. following clearance of the pathogen, most effector cells die, although a small fraction survives to establish a memory population. subsequent exposure to the same pathogen induces a rapid response of memory t cells and efficient elimination of the pathogen. although much is known about the cd8 t cell response, the pre ... | 2008 | 18097030 |
| constitutive activation of wnt signaling favors generation of memory cd8 t cells. | t cell factor-1 (tcf-1) and lymphoid enhancer-binding factor 1, the effector transcription factors of the canonical wnt pathway, are known to be critical for normal thymocyte development. however, it is largely unknown if it has a role in regulating mature t cell activation and t cell-mediated immune responses. in this study, we demonstrate that, like il-7ralpha and cd62l, tcf-1 and lymphoid enhancer-binding factor 1 exhibit dynamic expression changes during t cell responses, being highly expres ... | 2010 | 20026746 |
| cd8 t cell cross-reactivity networks mediate heterologous immunity in human ebv and murine vaccinia virus infections. | in this study, we demonstrate complex networks of cd8 t cell cross-reactivities between influenza a virus and ebv in humans and between lymphocytic choriomeningitis virus and vaccinia virus in mice. we also show directly that cross-reactive t cells mediate protective heterologous immunity in mice. subsets of t cell populations reactive with one epitope cross-reacted with either of several other epitopes encoded by the same or the heterologous virus. human t cells specific to ebv-encoded bmlf1(28 ... | 2010 | 20164414 |
| formation of il-7ralphahigh and il-7ralphalow cd8 t cells during infection is regulated by the opposing functions of gabpalpha and gfi-1. | il-7 is essential for the survival of naive and memory t cells, and il-7 receptor alpha-chain (il-7ralpha) expression is dynamically regulated in activated cd8 t cells during acute viral and bacterial infections. most virus-specific cd8 t cells become il-7ralpha(low) and are relatively short-lived, but some escape il-7ralpha repression (referred to as il-7ralpha(high) memory precursor effector cells) and preferentially enter the memory cd8 t cell pool. how antiviral effector cd8 t cells regulate ... | 2008 | 18390712 |
| granzyme b-induced and caspase 3-dependent cleavage of gelsolin by mouse cytotoxic t cells modifies cytoskeleton dynamics. | granule-associated perforin and granzymes (gzms) are key effector molecules of cytotoxic t lymphocytes (tc cells) and natural killer cells and play a critical role in the control of intracellular pathogens and cancer. based on the notion that many gzms, including a, b, c, k, h, and m exhibit cytotoxic activity in vitro, all gzms are believed to serve a similar function in vivo. however, more recent evidence supports the concept that gzms are not unidimensional but, rather, possess non-cytotoxic ... | 2010 | 20395300 |
| serine protease inhibitor 6 protects inkt cells from self-inflicted damage. | the role played by apoptosis in the homeostasis of effector cells of the innate immune system is unclear. serine protease inhibitor 6 (spi6) is an inhibitor of granzyme b (grb) that protects cytotoxic t lymphocytes of the adaptive immune system from apoptosis. to determine whether spi6 also protects cells of the innate immune system from self-inflicted damage we have examined invariant nkt (inkt) cells. spi6-deficient inkt cells harbored increased levels of grb after tcr stimulation with the pbs ... | 2010 | 20543105 |
| high diversity and ancient common ancestry of lymphocytic choriomeningitis virus. | lymphocytic choriomeningitis virus (lcmv) is the prototype of the family arenaviridae. lcmv can be associated with severe disease in humans, and its global distribution reflects the broad dispersion of the primary rodent reservoir, the house mouse (mus musculus). recent interest in the natural history of the virus has been stimulated by increasing recognition of lcmv infections during pregnancy, and in clusters of lcmv-associated fatal illness among tissue transplant recipients. despite its publ ... | 2010 | 20587180 |
| reinvigorating exhausted hiv-specific t cells via pd-1-pd-1 ligand blockade. | the programmed death (pd)-1-pd-1 ligand (pd-l) pathway, which is part of the b7-cd28 family, consists of the pd-1 receptor and its two ligands pd-l1 and pd-l2. engagement of pd-1 by its ligands inhibits immune responses, and recent work has shown that pd-1 is highly expressed on exhausted t cells during chronic lymphocytic choriomeningitis virus (lcmv) infection in mice. blockade of this pathway reinvigorates the exhausted t cells, allowing them to expand and produce effector cytokines, raising ... | 2006 | 17000870 |
| microbial contaminations of laboratory mice and rats in taiwan from 2004 to 2007. | limited data are available on the pathogen status of contemporary rodent colonies in taiwan. here we summarized the rodent pathogen diagnostic records of the taiwan national laboratory animal center during a 4-y period that representing approximately 10% of the rodent colonies in taiwan. demand for pathogen diagnostic service increased continuously from 2004 to 2007, with a 20% increase each year. in 2007, more than 20% of the mouse colonies were positive for mouse parvovirus, mouse hepatitis vi ... | 2009 | 19653946 |
| anti-thymoglobulin (atg) treatment does not reverse type 1 diabetes in the acute virally induced rat insulin promoter-lymphocytic choriomeningitis virus (rip-lcmv) model. | immune modulators such as anti-thymoglobulin (atg) are under clinical evaluation for the treatment of type 1 diabetes (t1d). although such agents have cured t1d in the non-obese diabetic (nod) model, their clinical efficacy has been much lower. in order to improve the odds of successful translation from bench to bedside, we propose to evaluate this agent under more stringent conditions. here, we evaluated the capacity of atg to reverse t1d in the acute rat insulin promoter-lymphocytic choriomeni ... | 2011 | 21235534 |
| killing of targets by cd8 t cells in the mouse spleen follows the law of mass action. | it has been difficult to correlate the quality of cd8 t cell responses with protection against viral infections. to investigate the relationship between efficacy and magnitude of t cell responses, we quantify the rate at which individual cd8 effector and memory t cells kill target cells in the mouse spleen. using mathematical modeling, we analyze recent data on the loss of target cells pulsed with three different peptides from the mouse lymphocytic choriomeningitis virus (lcmv) in mouse spleens ... | 2011 | 21283669 |
| mouse granzyme k has pro-inflammatory potential. | granzymes (gzms) are key components of t-killer (tc) cells believed to mediate pro-apoptotic activities. recent evidence suggests that gzms also possess non-cytotoxic activities that contribute to host defense. in this study, we show that tc cells from lymphocytic choriomeningitis virus (lcmv)-infected wild-type (wt) and gzm a/b-deficient mice express similar levels of gzmk protein, with both mouse strains efficiently controlling infection. gzmk, in recombinant form or secreted by ex vivo-derive ... | 2011 | 21311565 |