| transient control of a virus-induced immunopathology by genetic immunosuppression. | the ability to control t cell reactivity using suicide genes opens new perspectives for the treatment of t cell-mediated diseases. the therapeutic effect is achieved by the selective killing of thymidine kinase gene-modified activated t cells by ganciclovir (gcv). this strategy has been shown to control t cell alloreactivity efficiently after bone marrow or solid organ transplantation. here, we aimed to determine whether an immunopathological process induced by a viral infection could be control ... | 2000 | 11021591 |
| induction of human immunodeficiency virus (hiv)-specific cd8 t-cell responses by listeria monocytogenes and a hyperattenuated listeria strain engineered to express hiv antigens. | induction of cell-mediated immunity may be essential for an effective aids vaccine. listeria monocytogenes is an attractive bacterial vector to elicit t-cell immunity to human immunodeficiency virus (hiv) because it specifically infects monocytes, key antigen-presenting cells, and because natural infection originates at the mucosa. immunization with recombinant l. monocytogenes has been shown to protect mice from lymphocytic choriomeningitis virus, influenza virus, and tumor inoculation. l. mono ... | 2000 | 11024127 |
| viral escape and the failure of cellular immune responses. | | 2000 | 11032545 |
| requirements for bone marrow-derived antigen-presenting cells in priming cytotoxic t cell responses to intracellular pathogens. | bone marrow (bm)-derived antigen-presenting cells (apcs) are potent stimulators of t cell immune responses. we investigated the requirements for antigen presentation by these cells in priming cytotoxic t lymphocyte (ctl) responses to intracellular bacterial and viral pathogens. [parent-->f(1)] radiation bm chimeras were constructed using c57bl/6 donors and (c57bl/6 x balb/c)f(1) recipients. infection of chimeric mice with either listeria monocytogenes or vaccinia virus expressing the nucleoprote ... | 2000 | 11034603 |
| bone marrow-derived antigen-presenting cells are required for the generation of cytotoxic t lymphocyte responses to viruses and use transporter associated with antigen presentation (tap)-dependent and -independent pathways of antigen presentation. | bone marrow (bm)-derived professional antigen-presenting cells (papcs) are required for the generation of cytotoxic t lymphocyte (ctl) responses to vaccinia virus and poliovirus. furthermore, these bm-derived papcs require a functional transporter associated with antigen presentation (tap). in this report we analyze the requirements for bm-derived papcs and tap in the initiation of ctl responses to lymphocytic choriomeningitis virus (lcmv) and influenza virus (flu). our results indicate a requir ... | 2000 | 11034604 |
| persistent virus infection despite chronic cytotoxic t-lymphocyte activation in gamma interferon-deficient mice infected with lymphocytic choriomeningitis virus. | the role of gamma interferon (ifn-gamma) in the permanent control of infection with a noncytopathic virus was studied by comparing immune responses in wild-type and ifn-gamma-deficient (ifn-gamma -/-) mice infected with a slowly invasive strain of lymphocytic choriomeningitis virus (lcmv armstrong). while wild-type mice rapidly cleared the infection, ifn-gamma -/- mice became chronically infected. virus persistence in the latter mice did not reflect failure to generate cytotoxic t-lymphocyte (ct ... | 2000 | 11044074 |
| viral meningitis. | enteroviruses account for 85 to 95% of all cases of aseptic meningitis, but the arboviruses and herpes simplex virus are also important etiologic agents. mumps, lymphocytic choriomeningitis virus, herpes zoster, human herpesvirus type 6, and influenza viruses are rare causes of meningitis. the virology, pathogenesis, epidemiology, clinical manifestations, diagnostic studies, and established and potential antiviral therapies for viral meningitis are discussed. a differential diagnosis of the asep ... | 2000 | 11051293 |
| immunosuppression and resultant viral persistence by specific viral targeting of dendritic cells. | among cells of the immune system, cd11c(+) and dec-205(+) splenic dendritic cells primarily express the cellular receptor (alpha-dystroglycan [alpha-dg]) for lymphocytic choriomeningitis virus (lcmv). by selection, strains and variants of lcmv that bind alpha-dg with high affinity are associated with virus replication in the white pulp, show preferential replication in a majority of cd11c(+) and dec-205(+) cells, cause immunosuppression, and establish a persistent infection. in contrast, viral s ... | 2000 | 11067874 |
| cutting edge: off cycling of tnf production by antigen-specific cd8+ t cells is antigen independent. | although they are known for their capacity to kill infected cells, ag-specific cd8(+) t cells elaborate other effector mechanisms, including tnf and ifn-gamma, that contribute to defense against infection. ag-specific cd8(+) t cells rapidly turn on and turn off ifn-gamma production in direct response to ag contact, presumably to minimize the potential immunopathology that could result from inappropriate secretion of this inflammatory mediator. in this study, we show, using in vitro propagated an ... | 2000 | 11067887 |
| neither b lymphocytes nor antibodies directed against self antigens of the islets of langerhans are required for development of virus-induced autoimmune diabetes. | we evaluated the role of the humoral arm of the immune response in causing or contributing to virus-induced diabetes. transgenic mice expressing the nucleoprotein (np) or glycoprotein (gp) of the lymphocytic choriomeningitis virus (lcmv) under control of the rat insulin promoter (rip) in pancreatic beta cells (rip-lcmv) and rip-lcmv mice with genetic dysfunction of b cells (rip-lcmv x micromt/micromt) were compared for development of diabetes after challenge with lcmv. after inoculation with lcm ... | 2000 | 11067957 |
| immunodeficiency of alymphoplasia mice (aly/aly) in vivo: structural defect of secondary lymphoid organs and functional b cell defect. | alymphoplasia mice (aly/aly) have been shown to be deficient for a nuclear factor-kappab-inducing kinase involved in signal transduction of lymphotoxin beta receptor (lt-betar) and of cd40, resulting in structural defects of secondary lymphoid organs and highly increased susceptibility to viral infections. we analyzed the anti-viral immune response of bone marrow chimeras (bmc) between aly/aly mice and (c57bl/6 x dba2)f1 mice (b6d2f1) to evaluate in vivo whether the structural defects of seconda ... | 2000 | 11069060 |
| expression of ly49a on t cells alters the threshold for t cell responses. | in this study we investigated the balance between activating and inhibitory signals during t cell activation. we have used transgenic mice in which cd8+ t cells expressed an inhibitory receptor, ly49a, and a specific activating alphabeta tcr. this tcr recognizes an lymphocytic choriomeningitis virus peptide in combination with h-2db. we observed a quantitative influence on cellular responses that depended upon the activating signals received through the tcr and the inhibitory signals received th ... | 2000 | 11069066 |
| protective long-term antibody memory by antigen-driven and t help-dependent differentiation of long-lived memory b cells to short-lived plasma cells independent of secondary lymphoid organs. | memory is a hallmark of immunity. memory carried by antibodies is largely responsible for protection against reinfection with most known acutely lethal infectious agents and is the basis for most clinically successful vaccines. however, the nature of long-term b cell and antibody memory is still unclear. b cell memory was studied here after infection of mice with the rabies-like cytopathic vesicular stomatitis virus, the noncytopathic lymphocytic choriomeningitis virus (armstrong and we), and af ... | 2000 | 11069289 |
| partial impairment of cytokine responses in tyk2-deficient mice. | to assess the role of the janus kinase (jak) family member tyk2, we have generated tyk2-/- mice. in contrast to other jaks, where inactivation leads to a complete loss of the respective cytokine receptor signal, tyk2-/- mice display reduced responses to ifnalpha/beta and il-12 and a selective deficiency in stat3 activation in these pathways. unexpectedly, ifngamma signaling is also impaired in tyk2-/- mice. tyk2-/- macrophages fail to produce nitric oxide upon lipopolysaccharide induction. tyk2- ... | 2000 | 11070173 |
| an antigenic threshold for maintaining human immunodeficiency virus type 1-specific cytotoxic t lymphocytes. | using the lymphocytic choriomeningitis virus (lcmv) model in mice, a number of studies show that memory cytotoxic t-lymphocyte (ctl) responses are maintained in the presence of continuous antigenic stimulation. yet, other groups found that memory ctl specific for lcmv could last for a lifetime in mice without viral antigens. thus, the extent to which an antigen is required for the maintenance of virus-specific ctl remains controversial. in humans, very few studies have been conducted to investig ... | 2000 | 11071274 |
| generalized immunosuppression: how viruses undermine the immune response. | following infection, a virus must battle against the host's immune response. viruses have developed many ways to escape immune surveillance and downregulate the host's immune response. some viruses cause a generalized immunosuppression, thereby inhibiting or depressing the immune response towards themselves as well as towards unrelated pathogens. this review will focus on the mechanisms involved in the three main human viral infections causing immunosuppression: measles, human immunodeficiency v ... | 2000 | 11078019 |
| virus-induced autoimmune diabetes: most beta-cells die through inflammatory cytokines and not perforin from autoreactive (anti-viral) cytotoxic t-lymphocytes. | autoimmune diabetes is caused by selective loss of insulin-producing pancreatic beta-cells. the main factors directly implicated in beta-cell death are autoreactive, cytotoxic (islet-antigen specific) t-lymphocytes (ctl), and inflammatory cytokines. in this study, we have used an antigen-specific model of virally induced autoimmune diabetes to demonstrate that even high numbers of autoreactive ctl are unable to lyse beta-cells by perforin unless major histocompatibility complex class i is upregu ... | 2000 | 11078446 |
| evolution of the t cell repertoire during primary, memory, and recall responses to viral infection. | many viral infections induce a broad repertoire of cd8(+) t cell responses that initiate recognition and elimination of infected cells by interaction of tcrs with viral peptides presented on infected cells by mhc class i proteins. following clearance of the infection, >90% of activated cd8(+) t cells die, leaving behind a stable pool of memory cd8(+) t cells capable of responding to subsequent infections with enhanced kinetics. to probe the mechanisms involved in the generation of t cell memory, ... | 2000 | 11086040 |
| potential pathways for regulation of nk and t cell responses: differential x-linked lymphoproliferative syndrome gene product sap interactions with slam and 2b4. | sap, the gene that is altered or absent in the x-linked lymphoproliferative syndrome (xlp), encodes a small protein that comprises a single sh2 domain and binds to the cell-surface protein slam which is present on activated or memory t and b cells. because defective nk cell activity also has been reported in xlp patients, we studied the sap gene in nk cells. sap was induced upon viral infection of scid mice and shown to be expressed in nk cells by in vitro culturing in the presence of il-2. more ... | 2000 | 11099315 |
| preservation of graft-versus-infection effects after suicide gene therapy for prevention of graft-versus-host disease. | the main complications following allogeneic hematopoietic stem cell transplantation are graft-versus-host disease and poor immune reconstitution leading to severe infections. mature donor t cells present in the transplant facilitate t cell reconstitution in adults, but also induce graft-versus-host disease, which itself impairs immune reconstitution. thus, infusing a large number of donor t cells with a diverse repertoire should accelerate functional immune reconstitution after transplantation, ... | 2000 | 11119419 |
| differences in affinity of binding of lymphocytic choriomeningitis virus strains to the cellular receptor alpha-dystroglycan correlate with viral tropism and disease kinetics. | alpha-dystroglycan (alpha-dg) was recently identified as a receptor for lymphocytic choriomeningitis virus (lcmv) and several other arenaviruses, including lassa fever virus (w. cao, m. d. henry, p. borrow, h. yamada, j. h. elder, e. v. ravkov, s. t. nichol, r. w. compans, k. p. campbell, and m. b. a. oldstone, science 282:2079-2081, 1998). data presented in this paper indicate that the affinity of binding of lcmv to alpha-dg determines viral tropism and the outcome of infection in mice. to char ... | 2001 | 11119613 |
| functionally inert hiv-specific cytotoxic t lymphocytes do not play a major role in chronically infected adults and children. | the highly sensitive quantitation of virus-specific cd8(+) t cells using major histocompatibility complex-peptide tetramer assays has revealed higher levels of cytotoxic t lymphocytes (ctls) in acute and chronic virus infections than were recognized previously. however, studies in lymphocytic choriomeningitis virus infection have shown that tetramer assays may include measurement of a substantial number of tetramer-binding cells that are functionally inert. such phenotypically silent ctls, which ... | 2000 | 11120778 |
| dendritic cell elimination as an assay of cytotoxic t lymphocyte activity in vivo. | we show in this paper that the survival of antigen-loaded dendritic cells in vivo may be used as a sensitive readout of ctl activity. we have previously shown that dendritic cells labeled with the fluorescent dye cfse and injected sub-cutaneously into mice migrate spontaneously to the draining lymph node where they persist for several days. in the presence of effector ctl responses, dendritic cells loaded with specific antigen rapidly disappear from the draining lymph node. in this paper we exte ... | 2000 | 11121552 |
| identification of sequences in the human peptide transporter subunit tap1 required for transporter associated with antigen processing (tap) function. | the heterodimeric peptide transporter associated with antigen processing (tap) consisting of the subunits tap1 and tap2 mediates the transport of cytosolic peptides into the lumen of the endoplasmic reticulum (er). in order to accurately define domains required for peptide transporter function, a molecular approach based on the construction of a panel of human tap1 mutants and their expression in tap1(-/-) cells was employed. the characteristics and biological activity of the various tap1 mutant ... | 2001 | 11133832 |
| role of cd28/cd80-86 and cd40/cd154 costimulatory interactions in host defense to primary herpes simplex virus infection. | dependence of the primary antiviral immune response on costimulatory interactions between cd28/cd80-86 and between cd40/cd154 (cd40 ligand) has been correlated with the extent of viral replication in two models of systemic infection, lymphocytic choriomeningitis virus and vesicular stomatitis virus. to determine the role of these costimulatory interactions in the context of an acute cytolytic, but locally replicating viral infection, herpes simplex virus (hsv) infection was assessed in mice that ... | 2001 | 11134274 |
| recombinant expression of lymphocytic choriomeningitis virus strain we glycoproteins: a single amino acid makes the difference. | cytoplasmic vector systems are generally used for expression of lymphocytic choriomeningitis virus (lcmv) proteins. however, we achieved high levels of cell surface glycoproteins using a standard nuclear expression plasmid. expression was independent of other lcmv proteins but was blocked by a missense mutation within the original lcmv(we) glycoprotein cdna. | 2001 | 11134321 |
| gene expression in antigen-specific cd8+ t cells during viral infection. | following infection with intracellular pathogens, ag-specific cd8(+) t cells become activated and begin to proliferate. as these cells become activated, they elaborate effector functions including cytokine production and cytolysis. after the infection has been cleared, the immune system returns to homeostasis through apoptosis of the majority of the ag-specific effector cells. the surviving memory cells can persist for extended periods and provide protection against reinfection. little is known ... | 2001 | 11145652 |
| viral infection causes rapid sensitization to lipopolysaccharide: central role of ifn-alpha beta. | lps is the major active agent in the pathogenesis of gram-negative septic shock. in this report we have studied the influence of concurrent viral infection on the outcome of lps-induced shock. we find that infection with vesicular stomatitis virus sensitizes mice to lps at an early time point following infection. treatment of mice with the chemical ifn inducer, polyinosinic:polycytidylic acid, has a similar effect. this hypersensitivity to lps correlated with hyperproduction of tnf-alpha in vivo ... | 2001 | 11145676 |
| variable effects of transgenic c-maf on autoimmune diabetes. | autoimmune diabetes is associated with t helper 1 polarization, but protection from disease can be provided by the application of t helper 2 (th2) cytokines. to test whether genetic manipulation of t-cells can provide protective th2 responses, we developed transgenic mice in which t-cells express the interleukin-4-specific transcription factor c-maf. when crossed with a transgenic model that combines a class ii restricted t-cell receptor specific for influenza hemagglutinin with islet beta-cell ... | 2001 | 11147792 |
| impairment of cd4(+) t cell responses during chronic virus infection prevents neutralizing antibody responses against virus escape mutants. | we have shown previously that neutralizing antibodies (nabs) are important contributors to the long-term immune control of lymphocytic choriomeningitis virus infection, particularly if cytotoxic t cell responses are low or absent. nevertheless, virus escape from the nab response due to mutations within the surface glycoprotein gene may subsequently allow the virus to persist. here we show that most of the antibody-escape viral mutants retain their immunogenicity. we present evidence that the fai ... | 2001 | 11157050 |
| independent regulation of lymphocytic choriomeningitis virus-specific t cell memory pools: relative stability of cd4 memory under conditions of cd8 memory t cell loss. | infection of mice with a series of heterologous viruses causes a reduction of memory cd8(+) t cells specific to viruses from earlier infections, but the fate of the virus-specific memory cd4(+) t cell pool following multiple virus infections has been unknown. we have previously reported that the virus-specific cd4(+) th precursor (thp) frequency remains stable into long-term immunity following lymphocytic choriomeningitis virus (lcmv) infection. in this study, we questioned whether heterologous ... | 2001 | 11160196 |
| a role for ifn-alpha beta in virus infection-induced sensitization to endotoxin. | underlying viral infections can heighten sensitivity and worsen cytokine-mediated disease following secondary inflammatory challenges. mechanisms for this are poorly understood. the impact of the innate response to lymphocytic choriomeningitis virus (lcmv) infection on sensitivity to endotoxin (lps) was investigated. compared with uninfected mice, infection with lcmv for 2-days-sensitized mice to lps by approximately 2-fold for lethality and by 2- to 6-fold for serum tnf-alpha levels. priming fo ... | 2001 | 11160329 |
| using recombinant coxsackievirus b3 to evaluate the induction and protective efficacy of cd8+ t cells during picornavirus infection. | coxsackievirus b3 (cvb3) is a common human pathogen that has been associated with serious diseases including myocarditis and pancreatitis. to better understand the effect of cytotoxic t-lymphocyte (ctl) responses in controlling cvb3 infection, we have inserted well-characterized ctl epitopes into the cvb3 genome. constructs were made by placing the epitope of interest upstream of the open reading frame encoding the cvb3 polyprotein, separated by a poly-glycine linker and an artificial 3cpro/3cdp ... | 2001 | 11160741 |
| molecular and functional dissection of the h-2db-restricted subdominant cytotoxic t-cell response to lymphocytic choriomeningitis virus. | infection of h-2b mice with lymphocytic choriomeningitis virus (lcmv) generates an h-2db-restricted cytotoxic t-lymphocyte (ctl) response whose subdominant component is directed against the gp92-101 (csannshhyi) epitope. the aim of this study was to identify the functional parameters accounting for this subdominance. we found that the two naturally occurring (genetically encoded and posttranslationally modified) forms of lcmv gp92-101 were immunogenic, did not act as t-cell antagonists, and boun ... | 2001 | 11160751 |
| predicting the dynamics of antiviral cytotoxic t-cell memory in response to different stimuli: cell population structure and protective function. | this paper examines the numerical and functional consequences of various stimuli on antiviral cd8+ t-cell memory using a mathematical model. the model is based upon biological evidence from the murine model of infection with lymphocytic choriomeningitis virus (lcmv) that the phenotype of immunological memory represents low-level responses driven by various stimuli, and the memory ctl population is partitioned between resting, cycling and effector cells. these subpopulations differ in their lifes ... | 2001 | 11168627 |
| mhc class i-restricted killing of neurons by virus-specific cd8+ t lymphocytes is effected through the fas/fasl, but not the perforin pathway,. | induction of mhc class i genes in neurons of the central nervous system requires signals by pro-inflammatory cytokines, in particular ifn-gamma, and the blockade of electric activity, which is known to suppress induction of mhc related genes in a highly ordered, but unusual fashion [1], [2]. the present experiments explore the immunological function of neuronal mhc class i antigens expressed under permissive conditions. mhc class i proteins were induced in electrically silenced murine hippocampa ... | 2000 | 11169405 |
| interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic cd8+ t-cell responses. | the mechanism underlying suppression of immune responses by interleukin-4 (il-4) has remained unexplained. here we show that the antigen-presenting dendritic cell is central to counter-regulation of autoimmune disease by il-4. il-4 acts at the locus of the dendritic cell to decrease the cytolytic t-cell response, preventing autoimmunity. stimulation of cytotoxic precursors by antigen pulsed dendritic cells induces their differentiation but the process is blocked by il-4. il-4-influenced dc produ ... | 2001 | 11175852 |
| [quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24 well plates] | titres of lymphocytic choriomeningitis virus (lcmv) were determined on adherent fibroblast cell lines in 24, respectively 96 well plates. after absorption of virus by cells and 48 h incubation under a methylcellulose overlay, cell monolayers were fixed with 4% formaldehyde in phosphate buffered saline, permeabilized by incubating in 0.5% triton x-100 in balanced salt solution and then stained with a monoclonal rat anti-lcmv and a peroxidase labeled second stage antibody. the sensitivity of the a ... | 1993 | 11178349 |
| normal pathogen-specific immune responses mounted by ctla-4-deficient t cells: a paradigm reconsidered. | ctla-4 is a critical negative regulator of t cell responses and ctla-4-deficient (ctla-4(-/-)) mice die of a lymphproliferative disease. nevertheless, rag-2-deficient mice reconstituted with a mixture of ctla-4(-/-) and normal (ctla-4(+/+)) bone marrow survive in the absence of any signs of disease, although 50% of their t cells do not express ctla-4. using such mixed chimeras, we analyzed the role of ctla-4 in specific t cell responses to lymphocytic choriomeningitis virus, leishmania major and ... | 2001 | 11180109 |
| host factors influencing viral persistence. | with the aim of characterizing the antiviral immune response to a non-cytocidal virus, we studied the outcome of lymphocytic choriomeningitis virus infection in a number of gene knockout mouse strains. two virus strains differing markedly in their capacity to spread and replicate inside the murine host were used. our results reveal that very different outcomes may be observed depending on virus strain and immunocompetence of the host. thus while cd4+ cells are not critical during the initial pha ... | 2000 | 11186304 |
| hypercholesterolemia exacerbates virus-induced immunopathologic liver disease via suppression of antiviral cytotoxic t cell responses. | the immune system has to be optimally balanced to be highly effective against infections with cytopathic microbial pathogens and must guarantee efficient destruction of cells infected with noncytopathic agents while leaving the integrity of noninfected cells largely unaltered. we describe here the effects of genetically induced hypercholesterolemia on cellular immunity in apolipoprotein e (apoe(-/-)) and low density lipoprotein receptor-deficient (ldlr(-/-)) mice during infection with the hepato ... | 2001 | 11207293 |
| depletion of cd4+ t cells precipitates immunopathology in immunodeficient mice infected with a noncytocidal virus. | ifn-gamma-deficient (ifn-gamma(-/-)) mice inoculated with intermediate doses of a slowly replicating strain of lymphocytic choriomeningitis virus become chronically infected. in such mice a hypercompensated ctl response is observed that partially controls virus replication. here we have investigated whether cd4(+) th cells are required to establish and maintain this new equilibrium. the absence of ifn-gamma does not impair the generation of il-2-producing cd4(+) cells, and depletion of these cel ... | 2001 | 11207295 |
| the viral transmembrane superfamily: possible divergence of arenavirus and filovirus glycoproteins from a common rna virus ancestor. | recent studies of viral entry proteins from influenza, measles, human immunodeficiency virus, type 1 (hiv-1), and ebola virus have shown, first with molecular modeling, and then x-ray crystallographic or other biophysical studies, that these disparate viruses share a coiled-coil type of entry protein. | 2001 | 11208257 |
| disruption of differentiated functions during viral infection in vivo. v. mapping of a locus involved in susceptibility of mice to growth hormone deficiency due to persistent lymphocytic choriomeningitis virus infection. | lymphocytic choriomeningitis virus (lcmv) armstrong strain selectively and persistently infects the majority of growth hormone (gh) producing cells in the anterior lobe of pituitary glands of c3h/st mice but negligibly infects gh producing cells of balb/wehi mice (oldstone et al., virology 142, 175--182, 1985; oldstone et al., science 218, 1125--1127, 1982). although infected gh cells remain free of structural damage, disrupted initiation of gh transcription (klavinskis and oldstone, j. gen. vir ... | 2001 | 11222096 |
| cutting edge: ctls rapidly capture membrane fragments from target cells in a tcr signaling-dependent manner. | upon encounter of a ctl with a target cell carrying foreign ags, the tcr internalizes with its ligand, the peptide-mhc class i complex. however, it is unclear how this can happen mechanistically because mhc molecules are anchored to the target cell's surface via a transmembrane domain. by using antigenic peptides and lipids that were fluorescently labeled, we found that ctls promptly capture target cell membranes together with the antigenic peptide as well as various other surface proteins. this ... | 2001 | 11238601 |
| rapid peptide turnover and inefficient presentation of exogenous antigen critically limit the activation of self-reactive ctl by dendritic cells. | this study evaluated to what extent presentation of exogenously acquired self-ags via mhc class i molecules on dc might contribute to the activation of self-reactive ctl and subsequent development of autoimmune disease. we show here by using the rat insulin promotor lymphocytic choriomeningitis virus glycoprotein model of autoimmune diabetes that the activation of self-reactive ctl by dc after uptake of exogenous ag is very limited, first by the short half-life of mhc class i-associated peptides ... | 2001 | 11238607 |
| intralymphatic immunization enhances dna vaccination. | although dna vaccines have been shown to elicit potent immune responses in animal models, initial clinical trials in humans have been disappointing, highlighting a need to optimize their immunogenicity. naked dna vaccines are usually administered either i.m. or intradermally. the current study shows that immunization with naked dna by direct injection into a peripheral lymph node enhances immunogenicity by 100- to 1,000-fold, inducing strong and biologically relevant cd8(+) cytotoxic t lymphocyt ... | 2001 | 11248073 |
| [acute myelitis of an unusual cause in a child: the lymphocytic choriomeningitis virus]. | acute transverse myelitis is a rare disorder in childhood. it usually occurs as a post-infectious disease, but a precise infectious agent is identified in only 20% of cases. observation: the diagnosis of acute transverse myelitis was made in a 5.5-year-old girl who initially presented with left claude-bernard-horner syndrome and meningitis. a few days later, motor and sensory tetraparesia with bladder dysfunction was observed. magnetic resonance imaging showed a diffuse lesion in the medulla, wi ... | 2001 | 11270252 |
| structural and functional identification of major histocompatibility complex class i-restricted self-peptides as naturally occurring molecular mimics of viral antigens. possible role in cd8+ t cell-mediated, virus-induced autoimmune disease. | structural similarity (molecular mimicry) between viral epitopes and self-peptides can lead to the induction of autoaggressive cd4(+) as well as cd8(+) t cell responses. based on the flexibility of t cell receptor/antigen/major histocompatibility complex recognition, it has been proposed that a self-peptide could replace a viral epitope for t cell recognition and therefore participate in pathophysiological processes in which t cells are involved. to address this issue, we used, as a molecular mo ... | 2001 | 11278441 |
| cd11b expression as a marker to distinguish between recently activated effector cd8(+) t cells and memory cells. | cd8(+) t cells in different activation states have been difficult to identify phenotypically. in this study we have investigated whether mac-1 (cd11b) expression can be used as a criterion to distinguish between recently activated effector cells and memory cells belonging to the cd8(+) t cell subset. polyclonal virus-specific effector and memory cd8(+) t cells from lymphocytic choriomeningitis- and vesicular stomatitis virus-infected mice were visualized through staining for intracellular ifn-ga ... | 2001 | 11282998 |
| neutralizing antiviral antibodies reduce hematogenic viral spread but not antiviral cytotoxic t cell induction and subsequent immunopathology. | | 2001 | 11294679 |
| sap controls t cell responses to virus and terminal differentiation of th2 cells. | sh2d1a, which encodes signaling lymphocyte activation molecule (slam)-associated protein (sap), is altered in patients with x-linked lymphoproliferative disease (xlp), a primary immunodeficiency. sap-deficient mice infected with lymphocytic choriomeningitis virus had greatly increased numbers of cd8+ and cd4+ interferon-gamma-producing spleen and liver cells compared to wild-type mice. the immune responses of sap-deficient mice to infection with leishmania major together with in vitro studies sh ... | 2001 | 11323694 |
| 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 |
| tolerance induction with agonist peptides recognized by autoaggressive lymphocytes is transient: therapeutic potential for type 1 diabetes is limited and depends on time-point of administration, choice of epitope and adjuvant. | immunization with agonist peptides recognized by autoaggressive lymphocytes has been used successfully in several animal models for type 1 diabetes (t1d) or multiple sclerosis (ms) to prevent disease. depending on the timing of immunization, use of adjuvant and route of administration either elimination of autoaggressive t cells or induction of regulation reflected by cytokine shifts were described. since it was also reported that such agonist peptides could enhance autoimmunity by activating ag ... | 2001 | 11334483 |
| first outbreak of callitrichid hepatitis in germany: genetic characterization of the causative lymphocytic choriomeningitis virus strains. | callitrichid hepatitis (ch) is a highly fatal, rodent-borne zoonosis of new world primates (family callitrichidae) caused by lymphocytic choriomeningitis virus (lcmv). it is unclear whether virulence in callitrichidae is associated with specific genetic or phylogenetic markers of the virus as only a partial s rna sequence of a single ch-associated isolate is known. in a period of 10 months, three pygmy marmosets (cebuella pygmaea) and one goeldi's monkey (callimico goeldii) died from ch in a ger ... | 2001 | 11384220 |
| perforin-independent regulation of dendritic cell homeostasis by cd8(+) t cells in vivo: implications for adaptive immunotherapy. | we investigated here the effects of perforin on ctl responses during interaction of dendritic cells (dc) with cytotoxic t lymphocytes in vivo. using mhc class i tetramers complexed with the immunodominant ctl epitope of the lymphocytic choriomeningitis virus glycoprotein (lcmv-gp33), we followed the kinetics of dc-induced ctl responses. gp33-presenting dc induced rapid primary expansion of both perforin-competent and -deficient ctl with similar kinetics. secondary ctl responses in perforin-defic ... | 2001 | 11385622 |
| a dual role for tnf-alpha in type 1 diabetes: islet-specific expression abrogates the ongoing autoimmune process when induced late but not early during pathogenesis. | we report here that islet-specific expression of tnf-alpha can play a dual role in autoimmune diabetes, depending on its precise timing in relation to the ongoing autoimmune process. in a transgenic model (rat insulin promoter-lymphocytic choriomeningitis virus) of virally induced diabetes, tnf-alpha enhanced disease incidence when induced through an islet-specific tetracycline-dependent promoter system early during pathogenesis. blockade of tnf-alpha during this phase prevented diabetes complet ... | 2001 | 11390446 |
| attrition of bystander cd8 t cells during virus-induced t-cell and interferon responses. | experiments designed to distinguish virus-specific from non-virus-specific t cells showed that bystander t cells underwent apoptosis and substantial attrition in the wake of a strong t-cell response. memory cd8 t cells (cd8(+) cd44(hi)) were most affected. during acute viral infection, transgenic t cells that were clearly defined as non-virus specific decreased in number and showed an increase in apoptosis. also, use of lymphocytic choriomeningitis virus (lcmv) carrier mice, which lack lcmv-spec ... | 2001 | 11390598 |
| role of the promyelocytic leukemia protein pml in the interferon sensitivity of lymphocytic choriomeningitis virus. | lymphocytic choriomeningitis virus (lcmv) induces type i interferon (alpha and beta interferon [ifn-alpha and ifn-beta]) upon infection and yet is sensitive to the addition of type ii interferon (gamma interferon [ifn-gamma]) to the culture media. this sensitivity is biologically important because it correlates inversely with the ability of certain lcmv strains to persist in mice (d. moskophidis, m. battegay, m. a. bruendler, e. laine, i. gresser, and r. m. zinkernagel, j. virol. 68:1951-1955, 1 ... | 2001 | 11390623 |
| viral escape from the neutralizing antibody response: the lymphocytic choriomeningitis virus model. | in addition to cd8+ cytotoxic t lymphocyte (ctl) responses, neutralizing antibodies contribute substantially to the long-term immune control of noncytopathic viruses, as demonstrated during infection with the lymphocytic choriomeningitis virus (lcmv). the high virus load during the initial phase of an infection and the ability of this rna virus to spontaneously acquire mutations are important prerequisites for escaping an ongoing immune response. in this context, lcmv escape from the humoral res ... | 2001 | 11398962 |
| altered lymphocyte responses and cytokine production in mice deficient in the x-linked lymphoproliferative disease gene sh2d1a/dshp/sap. | we have introduced a targeted mutation in sh2d1a/dshp/sap, the gene responsible for the human genetic disorder x-linked lymphoproliferative disease (xlp). slam-associated protein (sap)-deficient mice had normal lymphocyte development, but on challenge with infectious agents, recapitulated features of xlp. infection of sap- mice with lymphocyte choriomeningitis virus (lcmv) or toxoplasma gondii was associated with increased t cell activation and ifn-gamma production, as well as a reduction of ig- ... | 2001 | 11404475 |
| common antiviral cytotoxic t-lymphocyte epitope for diverse arenaviruses. | members of the arenaviridae family have been isolated from mammalian hosts in disparate geographic locations, leading to their grouping as old world types (i.e., lymphocytic choriomeningitis virus [lcmv], lassa fever virus [lfv], mopeia virus, and mobala virus) and new world types (i.e., junin, machupo, tacaribe, and sabia viruses) (c. j. peters, m. j. buchmeier, p. e. rollin, and t. g. ksiazek, p. 1521-1551, in b. n. fields, d. m. knipe, and p. m. howley [ed.], fields virology, 3rd ed., 1996; p ... | 2001 | 11413293 |
| roles of tumour localization, second signals and cross priming in cytotoxic t-cell induction. | the vertebrate immune system has evolved to protect against infections that threaten survival before reproduction. clinically manifest tumours mostly arise after the reproductive years and somatic mutations allow even otherwise antigenic tumours to evade the attention of the immune system. moreover, the lack of immunological co-stimulatory molecules on solid tumours could result in t-cell tolerance; that is, the failure of t cells to respond. however, this may not generally apply. here we report ... | 2001 | 11429607 |
| cd4+ t-cell-epitope escape mutant virus selected in vivo. | mutations in viral genomes that affect t-cell-receptor recognition by cd8+ cytotoxic t lymphocytes have been shown to allow viral evasion from immune surveillance during persistent viral infections. although cd4+ t-helper cells are crucially involved in the maintenance of effective cytotoxic t-lymphocyte and neutralizing-antibody responses, their role in viral clearance and therefore in imposing similar selective pressures on the virus is unclear. we show here that transgenic virus-specific cd4+ ... | 2001 | 11433343 |
| murine cytomegalovirus is regulated by a discrete subset of natural killer cells reactive with monoclonal antibody to ly49h. | antiviral roles of natural killer (nk) cell subsets were examined in c57bl/6 mice infected with murine cytomegalovirus (mcmv) and other viruses, including lymphocytic choriomeningitis virus (lcmv), vaccinia virus (vv), and mouse hepatitis virus (mhv). each virus vigorously induced an nk cell infiltrate into the peritoneal cavity and liver, causing some redistributions of nk cell subsets defined by monoclonal antibody (mab) directed against ly49a, c/i, d, and g2. striking results were seen with a ... | 2001 | 11435470 |
| mucosal immunization with salmonella typhimurium expressing lassa virus nucleocapsid protein cross-protects mice from lethal challenge with lymphocytic choriomeningitis virus. | lassa fever virus (las) is transmitted to man by rodent carriers and is fatal in a third of untreated cases. our goal is to provide immune protection from lassa fever by mucosal vaccination. | 2001 | 11437313 |
| congenital lymphocytic choriomeningitis virus infection: decade of rediscovery. | lymphocytic choriomeningitis virus (lcmv) is an underdiagnosed fetal teratogen. this diagnosis should be considered for infants and children with unexplained hydrocephalus, micro- or macrocephaly, intracranial calcifications, chorioretinitis, and nonimmune hydrops. the immunofluorescent antibody test is the only reasonable, commercially available, screening diagnostic tool. the differential diagnosis of congenital lcmv infection includes toxoplasmosis, rubella, cytomegalovirus, herpes simplex vi ... | 2001 | 11438904 |
| delivery of multiple epitopes by recombinant detoxified adenylate cyclase of bordetella pertussis induces protective antiviral immunity. | cyaa, the adenylate cyclase toxin from bordetella pertussis, can deliver its n-terminal catalytic domain into the cytosol of a large number of eukaryotic cells and particularly into professional antigen-presenting cells. we have previously identified within the primary structure of cyaa several permissive sites at which insertion of peptides does not alter the ability of the toxin to enter cells. this property has been exploited to design recombinant cyaa toxoids capable of delivering major hist ... | 2001 | 11462005 |
| two overlapping subdominant epitopes identified by dna immunization induce protective cd8(+) t-cell populations with differing cytolytic activities. | subdominant cd8(+) t-cell responses contribute to control of several viral infections and to vaccine-induced immunity. here, using the lymphocytic choriomeningitis virus model, we demonstrate that subdominant epitopes can be more reliably identified by dna immunization than by other methods, permitting the identification, in the virus nucleoprotein, of two overlapping subdominant epitopes: one presented by l(d) and the other presented by k(d). this subdominant sequence confers immunity as effect ... | 2001 | 11462012 |
| multiple paths for activation of naive cd8+ t cells: cd4-independent help. | cd8(+) ctls play a pivotal role in immune responses against many viruses and tumors. two models have been proposed. the "three-cell" model focuses on the role of cd4(+) t cells, proposing that help is only provided to ctls by cd4(+) t cells that recognize ag on the same apc. the sequential "two-cell" model proposes that cd4(+) t cells can first interact with apcs, which in turn activate naive ctls. although these models provide a general framework for the role of cd4(+) t cells in mediating help ... | 2001 | 11466344 |
| 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 |
| the role of p53 in regulating antiviral t cell responses. | it is now well established that viral infections can induce large expansions of ag-specific cd8(+) t cells. these cells divide very rapidly with an estimated doubling time of approximately 6 h. when virus is cleared, the vast majority of these effector cd8 t cells undergo apoptosis. the remaining memory cells persist at constant levels and provide the basis for the accelerated recall response upon rechallenge. the molecular mechanisms that control the rapid proliferation and death of ag-specific ... | 2001 | 11466350 |
| functional avidity maturation of cd8(+) t cells without selection of higher affinity tcr. | unlike b cells, t cells lack the capacity to improve the affinity of their antigen receptors by somatic mutation. it is, therefore, believed that optimization of cellular immunity is mediated almost exclusively through selective expansion of t cells bearing receptors with the highest affinity for antigen. we show here that t cell responsiveness to peptide (termed "functional avidity") increased>50-fold during the early stages of viral infection. this indicated that t cells, like b cells, undergo ... | 2001 | 11477407 |
| pleiotropic effects of post-translational modifications on the fate of viral glycopeptides as cytotoxic t cell epitopes. | the fate of viral glycopeptides as cytotoxic t lymphocyte (ctl) epitopes is unclear. we have dissected the mechanisms of antigen presentation and ctl recognition of the peptide gp392-400 (wlvtngsyl) from the lymphocytic choriomeningitis virus (lcmv) and compared them with those of the previously reported gp92-101 antigen (csannshhyi). both gp392-400 and gp92-101 bear a glycosylation motif, are naturally n-glycosylated in the mature viral glycoproteins, bind to major histocompatibility complex h- ... | 2001 | 11479317 |
| critical role for alpha/beta and gamma interferons in persistence of lymphocytic choriomeningitis virus by clonal exhaustion of cytotoxic t cells. | under conditions of high antigenic load during infection with invasive lymphocytic choriomeningitis virus (lcmv) strains, virus can persist by selective clonal exhaustion of antigen-specific cd8(+) t cells. in this work we studied the down-regulation of the virus-specific cd8(+)-t-cell response during a persistent infection of adult mice, with particular emphasis on the contribution of the interferon response in promoting host defense. studies were conducted by infecting mice deficient in recept ... | 2001 | 11507186 |
| concerted action of the fasl/fas and perforin/granzyme a and b pathways is mandatory for the development of early viral hepatitis but not for recovery from viral infection. | cytotoxic t lymphocytes (ctl) play a major role in the recovery from primary viral infections and the accompanying tissue injuries. however, it is unclear to what extent the two main cytolytic pathways, perforin-granzyme a and b exocytosis and fas ligand (fasl)-fas interaction, contribute to these processes. here we have employed mouse strains with either spontaneous mutations or targeted gene defects in one or more components of either of the two cytolytic pathways to analyze the molecular basi ... | 2001 | 11507223 |
| pulmonary tumors in germfree mice: induction with urethan. | | 1970 | 11515033 |
| autoreactive diabetogenic t-cells in nod mice can efficiently expand from a greatly reduced precursor pool. | a broad repertoire of pancreatic beta-cell autoreactive t-cells normally contributes to the development of type 1 diabetes in nod mice. however, it has been unknown if a large reduction in the precursor pool from which autoreactive t-cells are drawn would inhibit the development of type 1 diabetes. to address this issue, we reduced the precursor frequency of autoreactive t-cells in nod mice through allelic exclusion induced by transgenic expression of an h2-db class i-restricted t-cell receptor ... | 2001 | 11522664 |
| ring finger z protein of lymphocytic choriomeningitis virus (lcmv) inhibits transcription and rna replication of an lcmv s-segment minigenome. | arenaviruses have a bisegmented negative-strand rna genome whose proteomic capability is limited to only four polypeptides, namely, nucleoprotein (np), surface glycoprotein (gp) that is proteolytically processed into gp1+gp2, polymerase (l), and a small (11-kda) ring finger protein (z). the role of z during the lymphocytic choriomeningitis virus (lcmv) life cycle is poorly understood. we investigated the function of z in virus transcription and replication by using a reverse genetic system for t ... | 2001 | 11533204 |
| 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 |
| effector differentiation is not prerequisite for generation of memory cytotoxic t lymphocytes. | the lineage relationship between short-lived effector t cells and long-lived memory cells is not fully understood. we have described t-gfp mice previously, in which naive and early activated t cells express gfp uniformly, whereas cells that have differentiated into effector cytotoxic t cells selectively lose gfp expression. here we studied antigen-specific cd8 t cell differentiation using t-gfp mice crossed to the tcr transgenic (tg) mice p14 (specific for the lymphocytic choriomeningitis virus ... | 2001 | 11560956 |
| is activation of autoreactive lymphocytes always detrimental? viral infections and regulatory circuits in autoimmunity. | | 2001 | 11569412 |
| low level viral persistence after infection with lcmv: a quantitative insight through numerical bifurcation analysis. | many important viruses persist at very low levels in the body in the face of host immunity, and may influence the maintenance of this state of 'infection immunity'. to analyse low level viral persistence in quantitative terms, we use a mathematical model of antiviral cytotoxic t lymphocyte (ctl) response to lymphocytic choriomeningitis virus (lcmv). this model, described by a non-linear system of delay differential equations (ddes), is studied using numerical bifurcation analysis techniques for ... | 2001 | 11576559 |
| zooming in on the hydrophobic ridge of h-2d(b): implications for the conformational variability of bound peptides. | class i major histocompatibility complex (mhc) molecules, which display intracellularly processed peptides on the cell surface for scanning by t-cell receptors (tcrs), are extraordinarily polymorphic. mhc polymorphism is believed to result from natural selection, since individuals heterozygous at the corresponding loci can cope with a larger number of pathogens. here, we present the crystal structures of the murine mhc molecule h-2d(b) in complex with the peptides gp276 and np396 from the lympho ... | 2001 | 11580250 |
| papillomavirus pseudovirus: a novel vaccine to induce mucosal and systemic cytotoxic t-lymphocyte responses. | intestinal mucosa is a portal for many infectious pathogens. systemic immunization, in general, does not induce a cytotoxic t-lymphocyte (ctl) response at the mucosal surface. because papillomavirus (pv) naturally infects mucosa and skin, we determined whether pv pseudovirus, i.e., pv-like particles in which unrelated dna plasmids are packaged, could generate specific mucosal immunity. we found that the pseudovirus that encoded the lymphocytic choriomeningitis virus gp33 epitope induced a strong ... | 2001 | 11581382 |
| cd4(+) t cells induced by a dna vaccine: immunological consequences of epitope-specific lysosomal targeting. | our previous studies have shown that targeting dna vaccine-encoded major histocompatibility complex class i epitopes to the proteasome enhanced cd8(+) t-cell induction and protection against lymphocytic choriomeningitis virus (lcmv) challenge. here, we expand these studies to evaluate cd4(+) t-cell responses induced by dna immunization and describe a system for targeting proteins and minigenes to lysosomes. full-length proteins can be targeted to the lysosomal compartment by covalent attachment ... | 2001 | 11581410 |
| enhancing t cell activation and antiviral protection by introducing the hiv-1 protein transduction domain into a dna vaccine. | protein transduction domains (ptd), which can transport proteins or peptides across biological membranes, have been identified in several proteins of viral, invertebrate, and vertebrate origin. here, we evaluate the immunological and biological consequences of including ptd in synthetic peptides and in dna vaccines that contain cd8(+) t cell epitopes from lymphocytic choriomeningitis virus (lcmv). synthetic ptd-peptides did not induce detectable cd8(+) t cell responses. however, fusion of an ope ... | 2001 | 11589830 |
| differential evolution and stability of epitope-specific cd8(+) t cell responses in ebv infection. | murine models of lymphocytic choriomeningitis virus infection suggest that the memory cd8(+) t cell repertoire is reflective of the cd8(+) t cell repertoire generated during acute infection. less is known regarding the evolution of cd8(+) t cell repertoires during human viral infections. we therefore examined epitope-specific cd8(+) t cell responses in a large cohort of individuals with acute through latent epstein-barr virus infection. using 16 of 20 published ebv epitopes restricted by hla-a2, ... | 2001 | 11591771 |
| distinct cd8 t cell functions mediate susceptibility to histoplasmosis during chronic viral infection. | it has long been recognized that some viral infections result in generalized immune suppression. in acute infections, this period of suppressed immunity is relatively short. however, chronic infections associated with a prolonged period of immune suppression present far greater risks. here, we examined the role of cd8 t cell responses following viral infection in immunity to systemic histoplasmosis. although wild-type mice with systemic histoplasmosis were able to control the infection, those si ... | 2001 | 11591785 |
| nk cell functions restrain t cell responses during viral infections. | nk cell functions for regulation of t cell responses were evaluated during acute viral infections. in vivo depletion studies established that the presence of nk cells in murine cytomegalovirus (mcmv)-infected immunocompetent mice negatively affected cd4 and cd8 t cell ifn-gamma expression, bromodeoxyuridine (brdu) incorporation, and expansion. to evaluate nk cell effects, under conditions when nk cells do not control viral replication, experiments were performed using lymphocytic choriomeningiti ... | 2001 | 11592081 |
| recruitment times, proliferation, and apoptosis rates during the cd8(+) t-cell response to lymphocytic choriomeningitis virus. | the specific cd8(+) t-cell response during acute lymphocytic choriomeningitis virus (lcmv) infection of mice is characterized by a rapid proliferation phase, followed by a rapid death phase and long-term memory. in balb/c mice the immunodominant and subdominant cd8(+) responses are directed against the np118 and gp283 epitopes. these responses differ mainly in the magnitude of the epitope-specific cd8(+) t-cell expansion. using mathematical models together with a nonlinear parameter estimation p ... | 2001 | 11602708 |
| 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 |
| molecular analysis of the interaction of lcmv with its cellular receptor [alpha]-dystroglycan. | alpha-dystroglycan (dg) has been identified as the cellular receptor for lymphocytic choriomeningitis virus (lcmv) and lassa fever virus (lfv). this subunit of dg is a highly versatile cell surface molecule that provides a molecular link between the extracellular matrix (ecm) and a beta-dg transmembrane component, which interacts with the actin-based cytoskeleton. in addition, dg exhibits a complex pattern of interaction with a wide variety of ecm and cellular proteins. in the present study, we ... | 2001 | 11604425 |
| memory cd8+ t cells in heterologous antiviral immunity and immunopathology in the lung. | a potent role for memory cd8+ t cells in heterologous immunity was shown with a respiratory mucosal model of viral infection. memory cd8+ t cells generated after lymphocytic choriomeningitis virus (lcmv) infection were functionally activated in vivo to produce interferon-gamma (ifn-gamma) during acute infection with vaccinia virus (vv). some of these antigen-specific memory cells selectively expanded in number, which resulted in modulation of the original lcmv-specific t cell repertoire. in addi ... | 2001 | 11668342 |
| induction of specific cd8+ memory t cells and long lasting protection following immunization with salmonella typhimurium expressing a lymphocytic choriomeningitis mhc class i-restricted epitope. | numerous studies have shown the potential of salmonella typhimurium as a vector for delivery of heterologous proteins for vaccination against other pathogens. earlier studies showed that the inefficient elicitation of mhc class i-restricted responses could limit the use of s. typhimurium as a heterologous antigen delivery vector for vaccination. we recently developed an approach to overcome this limitation by using a bacterial-encoded specialized protein secretion system, termed type iii, to del ... | 2001 | 11672924 |
| cutting edge: neosynthesis is required for the presentation of a t cell epitope from a long-lived viral protein. | ctls recognize peptide epitopes which are proteolytically generated by the proteasome and presented on mhc class i molecules. according to the defective ribosomal product (drip) hypothesis, epitopes originate from newly synthesized polypeptides which are degraded shortly after their translation. the drip hypothesis would explain how epitopes can be generated from long-lived proteins. we examined whether neosynthesis is required for presentation of the immunodominant epitope np118 of the lymphocy ... | 2001 | 11673482 |
| viral infections induce abundant numbers of senescent cd8 t cells. | viral infections are often accompanied by extensive proliferation of reactive cd8 t cells. after a defined number of divisions, normal somatic cells enter a nonreplicative stage termed senescence. in the present study we have identified the inhibitory killer cell lectin-like receptor g1 (klrg1) as a unique marker for replicative senescence of murine cd8 t cells. klrg1 expression was induced in a substantial portion (30-60%) of cd8 t cells in c57bl/6 mice infected with lymphocytic choriomeningiti ... | 2001 | 11673487 |
| characterization of virus-mediated inhibition of mixed chimerism and allospecific tolerance. | simultaneous blockade of the cd28 and cd40 t cell costimulatory pathways has been shown to effectively promote skin allograft survival in mice. furthermore, blockade of one or both of these pathways has played a central role in the development of strategies to induce mixed hematopoietic chimerism and allospecific tolerance. it has recently been observed that the beneficial effects of cd40 blockade and donor splenocytes in prolonging skin graft survival can be abrogated by some viral infections, ... | 2001 | 11673506 |
| schizophrenia and viral infection during neurodevelopment: a focus on mechanisms. | the task of defining schizophrenia pathogenesis has fascinated and frustrated researchers for nearly a century. in recent years, unprecedented advances from diverse fields of study have given credence to both viral and developmental theories. this review considers possible mechanisms by which viral and developmental processes may interact to engender schizophrenia. many of the current controversies in schizophrenia pathogenesis are reviewed in light of the viral hypothesis, including: epidemiolo ... | 2001 | 11673791 |
| generation of cellular immunity to lymphocytic choriomeningitis virus is independent of cd1d1 expression. | cd1 molecules are cell surface glycoproteins, structurally similar to major histocompatibility complex (mhc) class i molecules. the murine cd1d1 molecule has been shown to be essential for the positive selection of a unique subpopulation of t cells [the natural killer (nk) t cells], as cd1d1-deficient mice lack nk t cells. these cells have recently been suggested to play an important role in the induction of innate immunity (i.e. nk cells) and the regulation of immune homeostasis. as such, it wa ... | 2001 | 11683957 |