| il-10, t cell exhaustion and viral persistence. | viral infections can have one of two outcomes: control of viral replication and acute infection or viral persistence and chronic infection. it is clear that both pathogen and host characteristics influence the acute versus chronic outcome of viral infection. the early events in the host immune response that favor immunosuppression and viral persistence, however, have remained poorly understood. using the well-characterized mouse model of acute versus chronic lymphocytic choriomeningitis virus (l ... | 2007 | 17336072 |
| serpin-6 expression protects embryonic stem cells from lysis by antigen-specific ctl. | the immune response to embryonic stem (es) cells is still poorly understood. in this study, we addressed the adaptive cellular immune response to undifferentiated and differentiated es cells infected with lymphocytic choriomeningitis virus (lcmv), a vertically transmitted pathogen in mice and humans. in contrast to the prevailing view, we found that undifferentiated and differentiated murine es cells express mhc class i molecules, although at low levels. when cocultured with lcmv-infected es cel ... | 2007 | 17339433 |
| no essential role for tripeptidyl peptidase ii for the processing of lcmv-derived t cell epitopes. | the proteasome is critically involved in the production of mhc class i-restricted t cell epitopes. approximately 20% of all peptides generated by the proteasome are too large for direct presentation by mhc class i molecules. reits et al. (immunity 2004. 20: 495-506) suggested that a major portion of proteasomal products are larger than 15 amino acids and require further degradation by the tripeptidyl peptidase ii (tppii) before becoming ligands of mhc class i molecules. using the well-characteri ... | 2007 | 17357105 |
| impaired nfat nuclear translocation results in split exhaustion of virus-specific cd8+ t cell functions during chronic viral infection. | in persistent viral infections, the host's immune system is challenged by the constant exposure to antigen, potentially causing continuous activation of cd8(+) t cells with subsequent immunopathology. here we demonstrate, for experimental chronic lymphocytic choriomeningitis virus and human hiv infection, that upon prolonged in vivo exposure to antigen, tcr-triggered ca(2+) flux, degranulation, and cytotoxicity are maintained on a cellular level, whereas cytokine production is severely impaired ... | 2007 | 17360564 |
| old world and clade c new world arenaviruses mimic the molecular mechanism of receptor recognition used by alpha-dystroglycan's host-derived ligands. | alpha-dystroglycan (dg) is an important cellular receptor for extracellular matrix (ecm) proteins and also serves as the receptor for old world arenaviruses lassa fever virus (lfv) and lymphocytic choriomeningitis virus (lcmv) and clade c new world arenaviruses. in the host cell, alpha-dg is subject to a remarkably complex pattern of o glycosylation that is crucial for its interactions with ecm proteins. two of these unusual sugar modifications, protein o mannosylation and glycan modifications i ... | 2007 | 17360738 |
| broad-spectrum antiviral activity of small interfering rna targeting the conserved rna termini of lassa virus. | small interfering rnas targeting the conserved rna termini upstream of np and l gene were found to reduce reporter gene expression from lassa virus replicon and lassa virus mrna expression construct and to inhibit replication of different lassa virus strains, lymphocytic choriomeningitis virus, and mopeia virus in cell culture. | 2007 | 17371814 |
| a suspenseful game of 'hide and seek' between virus and host. | as part of the most important contributions to the understanding of viral immunity, michael oldstone recounts his pioneering work on lymphocytic choriomeningitis virus. | 2007 | 17375090 |
| cytotoxic t cell-mediated diabetes in rip-cd80 transgenic mice: autoantigen peptide sensitivity and fine specificity. | rodent immune-mediated diabetes model studies have advanced understanding of beta cell-specific t cell responses, and the testing of therapeutic approaches. we have used an inducible diabetes model based on rat insulin promotor (rip)-driven expression of cd80 (b7-1) on pancreatic beta cells. using these mice, we have established that immunizing with a single autoantigen can promote progressive islet inflammation and eventually t cell-mediated diabetes. we now describe a potent immunization proto ... | 2007 | 17376836 |
| mapping the landscape of the lymphocytic choriomeningitis virus stable signal peptide reveals novel functional domains. | the stable signal peptide (ssp) of the lymphocytic choriomeningitis virus surface glycoprotein precursor has several unique characteristics. the ssp is unusually long, at 58 amino acids, and contains two hydrophobic domains, and its sequence is highly conserved among both old and new world arenaviruses. to better understand the functions of the ssp, a panel of point and deletion mutants was created by in vitro mutagenesis to target the highly conserved elements within the ssp. we were also able ... | 2007 | 17376927 |
| genetic identification of kodoko virus, a novel arenavirus of the african pigmy mouse (mus nannomys minutoides) in west africa. | genetic evidence of a novel arenavirus species related to but distinct from lymphocytic choriomeningitis virus (lcmv) was obtained from a rodent belonging to an endemic african subgenus of mus (nannomys). the phylogenetic position among old world arenaviruses of this new arenavirus, named kodoko virus, was reconstructed based on l and np genes sequences. the finding of an old world arenavirus related to lcmv outside the known geographical range of lcmv in a novel rodent species reveals new insig ... | 2007 | 17382366 |
| minimal impact of a de novo-expressed beta-cell autoantigen on spontaneous diabetes development in nod mice. | during an autoimmune process, the autoaggressive response spreads from the initiating autoantigen to other antigens expressed in the target organ. based on evidence from experimental models for multiple sclerosis, such "antigenic spreading" can play an important role in the exacerbation of clinical disease. we evaluated whether pathogenesis of spontaneous diabetes in nod mice could be accelerated in a similar way when a novel autoantigen was expressed in pancreatic beta-cells. unexpectedly, we f ... | 2007 | 17395746 |
| indirect regulation of cd4 t-cell responses by tumor necrosis factor receptors in an acute viral infection. | despite the well-recognized importance of cd4 t-cell help in the induction of antibody production and cytotoxic-t-lymphocyte responses, the regulation of cd4 t-cell responses is not well understood. using mice deficient for tnf receptor i (tnfr i) and/or tnfr ii, we show that tnfr i and tnfr ii play redundant roles in down regulating the expansion of cd4 t cells during an acute infection of mice with lymphocytic choriomeningitis virus (lcmv). adoptive transfer experiments using t-cell-receptor t ... | 2007 | 17409152 |
| cure of chronic viral infection by neutralizing antibody treatment. | persistent infections can pose severe health risks. in many cases individuals fail to clear the virus and consequently chronic infection, often associated with severe immunopathology, occurs. for some chronic infections it is known that systemic il-10 production can be increased. however, it is unclear, whether il-10 affects the outcome of infection, amount of immunopathology and could be the actual cause for persistence. conventional interferons (ifn) or anti-viral immunotherapies attempting to ... | 2007 | 17412296 |
| antiviral cd4+ memory t cells are il-15 dependent. | survival and intermittent proliferation of memory cd4(+) and cd8(+) t cells appear to be controlled by different homeostatic mechanisms. in particular, contact with interleukin (il)-15 has a decisive influence on memory cd8(+) cells, but not memory cd4(+) cells. past studies of memory cd4(+) cells have relied heavily on the use of naturally occurring memory phenotype (mp) cells as a surrogate for antigen (ag)-specific memory cells. however, we show here that mp cd4(+) cells contain a prominent s ... | 2007 | 17420265 |
| viral antigen and extensive division maintain virus-specific cd8 t cells during chronic infection. | efficient maintenance of memory cd8 t cells is central to long-term protective immunity. il-7- and il-15-driven homeostatic proliferation is essential for long-term memory cd8 t cell persistence after acute infections. during chronic infections, however, virus-specific cd8 t cells respond poorly to these cytokines. yet, virus-specific cd8 t cells often persist for long periods of time during chronic infections. we have addressed this apparent paradox by examining the mechanism for maintaining vi ... | 2007 | 17420267 |
| jinx, an mcmv susceptibility phenotype caused by disruption of unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis. | mouse cytomegalovirus (mcmv) susceptibility often results from defects of natural killer (nk) cell function. here we describe jinx, an n-ethyl-n-nitrosourea-induced mcmv susceptibility mutation that permits unchecked proliferation of the virus, causing death. in jinx homozygotes, activated nk cells and cytotoxic t lymphocytes (ctls) fail to degranulate, although they retain the ability to produce cytokines, and cytokine levels are markedly elevated in the blood of infected mutant mice. jinx was ... | 2007 | 17420270 |
| suppression of cell-mediated immunity by a donor-transmitted lymphocytic choriomeningitis virus in a kidney transplant recipient. | infection with lymphocytic choriomeningitis virus (lcmv) in rodents, the primary host, is known to cause suppression of cell-mediated immunity. serial determinations using a functional cell-mediated immune assay in a kidney transplant recipient with donor-transmitted lcmv also suggested profound suppression of cellular immunity. this suppression persisted in spite of reduction of immunosuppression. with the clearance of the virus there was reconstitution of the cellular immune response. | 2007 | 17428276 |
| serological survey of virus infection among wild house mice (mus domesticus) in the uk. | the serological prevalence of 13 murine viruses was surveyed among 103 wild-caught and 51 captive-bred house mice (mus domesticus), originating from several trapping locations in northwest england, using blood samples obtained during routine health screening of an established wild mouse colony. a high proportion of recently caught wild mice were seropositive for mouse hepatitis virus (86%), mouse cytomegalovirus (79%), mouse thymic virus (78%), mouse adenovirus (68%), mouse parvovirus (59%) and ... | 2007 | 17430622 |
| antigen presentation by nonhemopoietic cells amplifies clonal expansion of effector cd8 t cells in a pathogen-specific manner. | professional apcs of hemopoietic-origin prime pathogen-specific naive cd8 t cells. the primed cd8 t cells can encounter ag on infected nonhemopoietic cell types. whether these nonhemopoietic interactions perpetuate effector t cell expansion remains unknown. we addressed this question in vivo, using four viral and bacterial pathogens, by comparing expansion of effector cd8 t cells in bone marrow chimeric mice expressing restricting mhc on all cell types vs mice that specifically lack restricting ... | 2007 | 17442964 |
| a retroviral packaging cell line for pseudotype vectors based on glioma-infiltrating progenitor cells. | early clinical trials for gene therapy of human gliomas with retroviral packaging cells (pc) have been hampered by low transduction efficacy and lack of dissemination of pc within the tumor. in the current approach, these issues have been addressed by creating a stable packaging cell line for retroviral vectors pseudotyped with glycoproteins of lymphocytic choriomeningitis virus (lcmv) based on tumor-infiltrating progenitor cells. | 2007 | 17474071 |
| rapid and sustained cd4(+) t-cell-independent immunity from adenovirus-encoded vaccine antigens. | many novel vaccine strategies rely on recombinant viral vectors for antigen delivery, and adenovirus vectors have emerged among the most potent of these. in this report, we have compared the immune response induced through priming with adenovirus vector-encoded full-length viral protein to that elicited with an adenovirus-encoded minimal epitope covalently linked to beta(2)-microglobulin. we demonstrate that the beta(2)-microglobulin-linked epitope induced an accelerated and augmented cd8(+) t-c ... | 2007 | 17485530 |
| differential role of il-2r signaling for cd8+ t cell responses in acute and chronic viral infections. | il-2 is a cytokine with multiple and even divergent functions; it has been described as a key cytokine for in vitro t cell proliferation but is also essential for down-regulating t cell responses by inducing activation-induced cell death as well as regulatory t cells. the in vivo analysis of il-2 function in regulating specific t cell responses has been hampered by the fact that mice deficient in il-2 or its receptors develop lymphoproliferative diseases and/or autoimmunity. here we generated ch ... | 2007 | 17492805 |
| protracted course of lymphocytic choriomeningitis virus we infection in early life: induction but limited expansion of cd8+ effector t cells and absence of memory cd8+ t cells. | viral infections in human infants frequently follow a protracted course, with higher viral loads and delayed viral clearance compared to viral infections in older children. to identify the mechanisms responsible for this protracted pattern of infection, we developed an infant infection murine model using the well-characterized lymphocytic choriomeningitis virus (lcmv) we strain in 2-week-old balb/c mice. in contrast to adult mice, in which viral clearance occurred as expected 8 days after infect ... | 2007 | 17494081 |
| adenoviral vectors persist in vivo and maintain activated cd8+ t cells: implications for their use as vaccines. | cd8(+) t cell-numbers rapidly expand and then contract after exposure to their cognate antigen. here we show that the sustained frequencies of transgene product-specific cd8(+) t cells elicited by replication-defective adenovirus vectors are linked to persistence of low levels of transcriptionally active adenovirus vector genomes at the site of inoculation, in liver, and lymphatic tissues. continuously produced small amounts of antigen maintain fully active effector cd8(+) t cells, while also al ... | 2007 | 17510320 |
| analysis of the role of bleomycin hydrolase in antigen presentation and the generation of cd8 t cell responses. | long oligopeptides (>10 residues) are generated during the catabolism of cellular proteins in the cytosol. to be presented to t cells, such peptides must be trimmed by aminopeptidases to the proper size (typically 8-10 residues) to stably bind to mhc class i molecules. aminopeptidases also destroy epitopes by trimming them to even shorter lengths. bleomycin hydrolase (bh) is a cytosolic aminopeptidase that has been suggested to play a key role in generating mhc class i-presented peptides. we sho ... | 2007 | 17513741 |
| early blood profiles of virus infection in a monkey model for lassa fever. | acute arenavirus disease in primates, like lassa hemorrhagic fever in humans, begins with flu-like symptoms and leads to death approximately 2 weeks after infection. our goal was to identify molecular changes in blood that are related to disease progression. rhesus macaques (macaca mulatta) infected intravenously with a lethal dose of lymphocytic choriomeningitis virus (lcmv) provide a model for lassa virus infection of humans. blood samples taken before and during the course of infection were u ... | 2007 | 17522210 |
| mouse-to-human transmission of variant lymphocytic choriomeningitis virus. | a case of lymphocytic choriomeningitis virus (lcmv) infection led to investigation of the reservoir. lcmv was detected in mice trapped at the patient's home, and 12 isolates were recovered. genetic analysis showed that human and mouse lcmvs were identical and that this lcmv strain was highly divergent from previously characterized lcmv. | 2007 | 17552104 |
| clearance of an immunosuppressive virus from the cns coincides with immune reanimation and diversification. | once a virus infection establishes persistence in the central nervous system (cns), it is especially difficult to eliminate from this specialized compartment. therefore, it is of the utmost importance to fully understand scenarios during which a persisting virus is ultimately purged from the cns by the adaptive immune system. such a scenario can be found following infection of adult mice with an immunosuppressive variant of lymphocytic choriomeningitis virus (lcmv) referred to as clone 13. in th ... | 2007 | 17553158 |
| pet rodents and fatal lymphocytic choriomeningitis in transplant patients. | in april 2005, 4 transplant recipients became ill after receiving organs infected with lymphocytic choriomeningitis virus (lcmv); 3 subsequently died. all organs came from a donor who had been exposed to a hamster infected with lcmv. the hamster was traced back through a rhode island pet store to a distribution center in ohio, and more lcmv-infected hamsters were discovered in both. rodents from the ohio facility and its parent facility in arkansas were tested for the same lcmv strain as the 1 i ... | 2007 | 17553250 |
| hantavirus and arenavirus antibodies in persons with occupational rodent exposure. | rodents are the principal hosts of sin nombre virus, 4 other hantaviruses known to cause hantavirus pulmonary syndrome in north america, and the 3 north american arenaviruses. serum samples from 757 persons who had worked with rodents in north america and handled neotomine or sigmodontine rodents were tested for antibodies against sin nombre virus, whitewater arroyo virus, guanarito virus, and lymphocytic choriomeningitis virus. antibodies against sin nombre virus were found in 4 persons, agains ... | 2007 | 17553266 |
| congenital lymphocytic choriomeningitis virus infection: spectrum of disease. | lymphocytic choriomeningitis virus (lcmv) is a human pathogen and an emerging neuroteratogen. when the infection occurs during pregnancy, the virus can target and damage the fetal brain and retina. we examined the spectrum of clinical presentations, neuroimaging findings, and clinical outcomes of children with congenital lcmv infection. | 2007 | 17557350 |
| interleukin-10 plays an early role in generating virus-specific t cell anergy. | infection of mice with the armstrong strain of lymphocytic choriomeningitis virus (lcmvarm) leads to a robust immune response and efficient viral clearance. this is in contrast to infection with the variant strain lcmvclone13, which causes functional inactivation of effector t cells and viral persistence. the mechanism by which lcmvclone13 suppresses the antiviral immune response and persists in its host is unknown. | 2007 | 17570849 |
| peptide-activated double-negative t cells can prevent autoimmune type-1 diabetes development. | autoimmune diseases may develop because of defective maturation, activation, differentiation and function of regulatory t cells. previous studies have shown that exposure to donor antigen activates peripheral tcralphabeta+cd3+cd4-cd8-nk1.1-, double-negative (dn) t cells, which specifically suppress anti-donor t cells and enhance survival of skin and heart grafts from allogeneic and xenogeneic donors. however, the role of dn t cells in preventing t cell-mediated autoimmune disease is unknown. her ... | 2007 | 17578845 |
| arenavirus z-glycoprotein association requires z myristoylation but not functional ring or late domains. | generation of infectious arenavirus-like particles requires the virus ring finger z protein and surface glycoprotein precursor (gpc) and the correct processing of gpc into gp1, gp2, and a stable signal peptide (ssp). z is the driving force of arenavirus budding, whereas the gp complex (gpc), consisting of hetero-oligomers of ssp, gp1, and gp2, forms the viral envelope spikes that mediate receptor recognition and cell entry. based on the roles played by z and gp in the arenavirus life cycle, we h ... | 2007 | 17581989 |
| bim/bcl-2 balance is critical for maintaining naive and memory t cell homeostasis. | we examined the role of the antiapoptotic molecule bcl-2 in combating the proapoptotic molecule bim in control of naive and memory t cell homeostasis using bcl-2(-/-) mice that were additionally deficient in one or both alleles of bim. naive t cells were significantly decreased in bim(+/-)bcl-2(-/-) mice, but were largely restored in bim(-/-)bcl-2(-/-) mice. similarly, a synthetic bcl-2 inhibitor killed wild-type, but not bim(-/-), t cells. further, t cells from bim(+/-)bcl-2(-/-) mice died rapi ... | 2007 | 17591857 |
| preformed cd40 ligand exists in secretory lysosomes in effector and memory cd4+ t cells and is quickly expressed on the cell surface in an antigen-specific manner. | cd40 ligand (cd40l) is an essential effector cytokine for macrophage activation, dendritic cell licensing, and t-cell-dependent antibody responses. although cd40l is known to be made de novo following antigen recognition, several reports have described surface mobilization of preformed, intracellular cd40l in certain cd4(+) effector t cells. here we show that rapid surface expression of preformed cd40l following antigen recognition is a general property of both effector and memory cd4(+) t cells ... | 2007 | 17595332 |
| sequential polymicrobial infections lead to cns inflammatory disease: possible involvement of bystander activation in heterologous immunity. | vv(plp) is a recombinant vaccinia virus (vv) encoding myelin proteolipid protein (plp) that has been used to investigate molecular mimicry and autoimmunity. since virus infections can cause bystander activation, mice were first infected with vv(plp), and later challenged with wild-type vv, lymphocytic choriomeningitis virus (lcmv), or murine cytomegalovirus (mcmv). among the vv(plp)-primed mice, only mcmv challenge induced significant ki-67(+), cd3(+)t cell infiltration into the central nervous ... | 2007 | 17604850 |
| 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 |
| simian immunodeficiency virus vector pseudotypes differ in transduction efficiency and target cell specificity in brain. | lentiviral vectors have proven to be promising tools for transduction of brain cells in vivo and in vitro. in this study, we have examined the central nervous system (cns) transduction efficiencies and patterns of a self-inactivating simian immunodeficiency virus (sivmac)-derived lentiviral vector pseudotyped with glycoproteins from the vesicular stomatitis virus (vsv-g), the amphotropic murine leukemia virus (mlv4070aenv), the lymphocytic choriomeningitis virus (lcmv-gp), the ross river virus ( ... | 2007 | 17611586 |
| chronic lymphocytic choriomeningitis virus infection actively down-regulates cd4+ t cell responses directed against a broad range of epitopes. | activation of cd4(+) t cells helps establish and sustain cd8(+) t cell responses and is required for the effective clearance of acute infection. cd4-deficient mice are unable to control persistent infection and cd4(+) t cells are usually defective in chronic and persistent infections. we investigated the question of how persistent infection impacted pre-existing lymphocytic choriomeningitis virus (lcmv)-specific cd4(+) t cell responses. we identified class ii-restricted epitopes from the entire ... | 2007 | 17617598 |
| direct interferon-gamma signaling dramatically enhances cd4+ and cd8+ t cell memory. | studies in ifn-gamma-deficient mice suggest that the delivery of ifn-gamma to cd8(+) t cells early in virus infection programs their eventual contraction, thereby reducing the abundance of cd8(+) memory t cells. in this study, we show that such mice fail to completely eliminate virus infection and that, when evaluated without the confounding factor of persisting ag, both cd4(+) and cd8(+) t cells undergo profound contraction when they are unable to receive ifn-gamma signals. furthermore, the abu ... | 2007 | 17617612 |
| ccr5 and cxcr3 are dispensable for liver infiltration, but ccr5 protects against virus-induced t-cell-mediated hepatic steatosis. | ccr5 and cxcr3 are important molecules in regulating the migration of activated lymphocytes. thus, the majority of tissue-infiltrating t cells found in the context of autoimmune conditions and viral infections express ccr5 and cxcr3, and the principal chemokine ligands are expressed within inflamed tissues. accordingly, intervention studies have pointed to nonredundant roles of these receptors in models of allograft rejection, viral infection, and autoimmunity. in spite of this, considerable con ... | 2007 | 17626099 |
| development of recombinant nucleoprotein-based diagnostic systems for lassa fever. | diagnostic systems for lassa fever (lf), a viral hemorrhagic fever caused by lassa virus (lasv), such as enzyme immunoassays for the detection of lasv antibodies and lasv antigens, were developed using the recombinant nucleoprotein (rnp) of lasv (lasv-rnp). the lasv-rnp was expressed in a recombinant baculovirus system. lasv-rnp was used as an antigen in the detection of lasv-antibodies and as an immunogen for the production of monoclonal antibodies. the lasv-rnp was also expressed in hela cells ... | 2007 | 17634509 |
| cd8 t cell dysfunction during chronic viral infection. | clearance of primary infection often leads to the development of highly functional memory t cells capable of rapid and long-lasting protective immunity. by contrast, chronic infections can result in t cell dysfunction and poor pathogen control. in this review, we will discuss recent work that highlights two main types of t cell dysfunction during chronic infection: exhaustion of effector functions and altered memory t cell development. | 2007 | 17656078 |
| decreased tumor surveillance after adoptive t-cell therapy. | the effect of cancer immunotherapy on the endogenous immune response against tumors is largely unknown. therefore, we studied immune responses against murine tumors expressing the glycoprotein (gp) and/or nucleoprotein of lymphocytic choriomeningitis virus (lcmv) with or without adoptive t-cell therapy. in nontreated animals, ctls specific for different epitopes as well as lcmv-gp-specific antibodies contributed to tumor surveillance. adoptive immunotherapy with monoclonal ctls specific for lcmv ... | 2007 | 17671217 |
| 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 |
| role of direct effects of ifn-gamma on t cells in the regulation of cd8 t cell homeostasis. | it is well recognized that ifn-gamma plays a critical role in the control of cd8 t cell expansion and contraction during immune responses to several intracellular pathogens. however, our understanding of the mechanisms underlying the regulation of t cell fate by ifn-gamma is sorely incomplete. specifically, it is unclear whether regulation of cd8 t cell homeostasis occurs by a t cell intrinsic ifn-gamma pathway. in this study, we have determined the role of the direct effects of ifn-gamma on t c ... | 2007 | 17675470 |
| chronic immunodeficiency in mice lacking rasgrp1 results in cd4 t cell immune activation and exhaustion. | the ras-guanyl nucleotide exchange factor rasgrp1 is an important link between tcr-mediated signaling and the activation of ras and its downstream effectors. rasgrp1 is especially critical for the survival and differentiation of developing thymocytes whereas negative selection of thymocytes bearing an autoreactive tcr appears to be rasgrp1 independent. despite apparently normal central tolerance, rasgrp1(-/-) mice spontaneously acquire an acutely activated and proliferating cd4 t cell population ... | 2007 | 17675473 |
| fully mhc-disparate mixed hemopoietic chimeras show specific defects in the control of chronic viral infections. | the establishment of mixed allogeneic chimerism can induce donor-specific transplantation tolerance across full mhc barriers. however, a theoretical disadvantage of this approach is the possibility that the state of mixed chimerism might negatively affect the recipient's immune competence to control pathogens. previous studies using murine models have not supported this hypothesis, because they indicate that acute viral infections are cleared by chimeric animals with similar kinetics to that of ... | 2007 | 17675525 |
| a lymphocytic choriomeningitis virus glycoprotein variant that is retained in the endoplasmic reticulum efficiently cross-primes cd8(+) t cell responses. | recent studies indicate that t cell cross-priming preferentially occurs against long-lived, stable proteins. we have studied cross-priming by using the glycoprotein (gp) of lymphocytic choriomeningitis virus (lcmv), a protein that normally is not mhc class i cross-presented. this study shows that a c-terminally truncated, noncleavable variant of lcmv-gp led to the accumulation of stable, soluble gp trimers in the endoplasmic reticulum (er) of the antigen donor cell, and thereby converted lcmv-gp ... | 2007 | 17686978 |
| lymphocytic choriomeningitis virus infection of the developing brain: critical role of host age. | lymphocytic choriomeningitis virus (lcmv) is a common human pathogen that causes substantial injury to the developing brain when the infection occurs during pregnancy. however, among children with congenital lcmv infection, there is considerable variability in the site, nature, and severity of neuropathology and in the clinical outcome. we hypothesize that the variability in neuropathology and outcome is due to differences in the gestational timing of lcmv infection. | 2007 | 17696127 |
| early antibodies specific for the neutralizing epitope on the receptor binding subunit of the lymphocytic choriomeningitis virus glycoprotein fail to neutralize the virus. | lymphocytic choriomeningitis virus (lcmv) is a murine arenavirus whose glycoprotein consists of a transmembrane subunit (gp-2) and a receptor-binding subunit (gp-1). lcmv-neutralizing antibodies (nabs) are directed against a single site on gp-1 and occur 1 month after the infection of cytotoxic-t-lymphocyte (ctl) deficient mice. in wild-type mice, however, ctls control early infection, and weak nab titers emerge very late (after 70 to 150 days) if at all. production of recombinant gp-1 in native ... | 2007 | 17699567 |
| a role for tnf in limiting the duration of ctl effector phase and magnitude of cd8 t cell memory. | it is known that tnf-alpha (tnf) exerts distinct tissue-protective or -destructive effects in the pathogenesis of t cell-dependent immunopathology, depending on the context and amount of cytokine produced. to better understand the cellular mechanisms underlying the regulation of t cells by tnf, we have analyzed the role of tnf in regulating various facets of the antigen-specific cd8 t cell response to lymphocytic choriomeningitis virus (lcmv) in mice. we show that expansion and differentiation o ... | 2007 | 17704295 |
| dynamics of cd8+ t cell responses during acute and chronic lymphocytic choriomeningitis virus infection. | infection of mice with lymphocytic choriomeningitis virus (lcmv) is frequently used to study the underlying principles of viral infections and immune responses. we fit a mathematical model to recently published data characterizing ag-specific cd8+ t cell responses during acute (armstrong) and chronic (clone 13) lcmv infection. this allows us to analyze the differences in the dynamics of cd8+ t cell responses against different types of lcmv infections. for the four cd8+ t cell responses studied, ... | 2007 | 17709509 |
| cd8+ t cell activation is governed by tcr-peptide/mhc affinity, not dissociation rate. | binding of peptide/mhc (pmhc) complexes by tcr initiates t cell activation. despite long interest, the exact relationship between the biochemistry of tcr/pmhc interaction (particularly tcr affinity or ligand off-rate) and t cell responses remains unresolved, because the number of complexes examined in each independent system has been too small to draw a definitive conclusion. to test the current models of t cell activation, we have analyzed the interactions between the mouse p14 tcr and a set of ... | 2007 | 17709510 |
| complement-dependent enhancement of cd8+ t cell immunity to lymphocytic choriomeningitis virus infection in decay-accelerating factor-deficient mice. | decay-accelerating factor (daf, cd55) is a gpi-anchored membrane protein that regulates complement activation on autologous cells. in addition to protecting host tissues from complement attack, daf has been shown to inhibit cd4+ t cell immunity in the setting of model ag immunization. however, whether daf regulates natural t cell immune response during pathogenic infection is not known. we describe in this study a striking regulatory effect of daf on the cd8+ t cell response to lymphocytic chori ... | 2007 | 17709533 |
| lymphocytic choriomeningitis infection in neonataily thymectomized mice bearing diffusion chambers containing thymus. | normal, nonoperated swiss mice which had been inoculated intracerebrally with lymphocytic choriomeningitis virus showed a 100-percent mortality within 8 days after virus challenge. neonatally thymectomized mice, with or without empty intraperitoneal diffusion chambers, were protected from the lethal effects of the virus, with no animals dying within 14 days after inoculation. cell-tight millipore diffusion chambers containing newborn thymic tissue, implanted intraperitoneally into neonatally thy ... | 1963 | 17748162 |
| old world arenavirus infection interferes with the expression of functional alpha-dystroglycan in the host cell. | alpha-dystroglycan (alpha-dg) is an important cellular receptor for extracellular matrix (ecm) proteins as well as the old world arenaviruses lymphocytic choriomeningitis virus (lcmv) and the human pathogenic lassa fever virus (lfv). specific o-glycosylation of alpha-dg is critical for its function as receptor for ecm proteins and arenaviruses. here, we investigated the impact of arenavirus infection on alpha-dg expression. infection with an immunosuppressive lcmv isolate caused a marked reducti ... | 2007 | 17761532 |
| programmed death-1 (pd-1) defines a transient and dysfunctional oligoclonal t cell population in acute homeostatic proliferation. | the host responds to lymphopenic environments by acute homeostatic proliferation, which is a cytokine- and endogenous peptide-driven expansion of lymphocytes that restores the numbers and diversity of t cells. it is unknown how these homeostatically proliferating (hp) cells are ultimately controlled. using a system where lymphocytic choriomeningitis virus-immune c57bl/6 splenocytes were transferred into lymphopenic t cell-deficient hosts and allowed to reconstitute the environment, we defined th ... | 2007 | 17785507 |
| differential inhibition of type i interferon induction by arenavirus nucleoproteins. | we have documented that the nucleoprotein (np) of the prototypic arenavirus lymphocytic choriomeningitis virus is an antagonist of the type i interferon response. in this study we tested the ability of nps encoded by representative arenavirus species from both old world and new world antigenic groups to inhibit production of interferon. we found that, with the exception of tacaribe virus (tcrv), all nps tested inhibited activation of beta interferon and interferon regulatory factor 3 (irf-3)-dep ... | 2007 | 17804508 |
| signal peptide requirements for lymphocytic choriomeningitis virus glycoprotein c maturation and virus infectivity. | insertion of the lymphocytic choriomeningitis virus (lcmv) precursor glycoprotein c (gp-c) into the membrane of the endoplasmic reticulum is mediated by an unusual signal peptide (sp(gp-c)). it is comprised of 58 amino acid residues and contains an extended hydrophilic n-terminal region, two hydrophobic regions, and a short c-terminal region. after cleavage by signal peptidase, sp(gp-c) accumulates in cells and virus particles. in the present study, we identified the lcmv sp(gp-c) as being an es ... | 2007 | 17804515 |
| high basal stat4 balanced by stat1 induction to control type 1 interferon effects in natural killer cells. | the best-characterized type 1 interferon (ifn) signaling pathway depends on signal transducer and activator of transcription 1 (stat1) and stat2. the cytokines can, however, conditionally activate all stats. regulation of their access to particular signaling pathways is poorly understood. stat4 is important for ifn-gamma induction, and nk cells are major producers of this cytokine. we report that nk cells have high basal stat4 levels and sensitivity to type 1 ifn-mediated stat4 activation for if ... | 2007 | 17846149 |
| capture of membrane components via trogocytosis occurs in vivo during both dendritic cells and target cells encounter by cd8(+) t cells. | cytotoxic t lymphocytes recently stimulated by antigen-presenting cells (apc) display major histocompatibility class (mhc) i and ii molecules inherited from apc. we have previously reported that, in vitro, transfer of mhc molecules and several other proteins occurs through trogocytosis, i.e. the active acquisition of target cell membrane fragments by t lymphocytes. here, using the model of viral antigen lcmvgp33-41 recognition in transgenic p14 mice, we show that cd8(+) t cells perform trogocyto ... | 2007 | 17850589 |
| immune suppression or enhancement by cd137 t cell costimulation during acute viral infection is time dependent. | cd137 is expressed on activated t cells and ligands to this costimulatory molecule have clinical potential for amplifying cd8 t cell immunity to tumors and viruses, while suppressing cd4 autoimmune t cell responses. to understand the basis for this dichotomy in t cell function, cd4 and cd8 antiviral immunity was measured in lymphocytic choriomeningitis virus (lcmv) armstrong- or a/pr8/34 influenza-infected mice injected with anti-cd137 mabs. we found that the timing of administration of anti-cd1 ... | 2007 | 17853940 |
| superinfection exclusion in bhk-21 cells persistently infected with junín virus. | we characterized a persistently junín virus (junv)-infected bhk-21 cell line obtained by experimental infection with the xjcl3 strain. this cell line, named k3, produced low levels of virus in supernatants which were not influenced by the presence of defective interfering (di) particles after the first year of infection. k3 cells were able to exclude superinfection of the homologous junv and the antigenically related tacaribe virus (tcrv), whereas the non-related arenaviruses lymphocytic choriom ... | 2007 | 17872526 |
| viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection. | many chronic viral infections are marked by pathogen persistence and a generalized immunosuppression. the exact mechanisms by which this occurs are still unknown. using a mouse model of persistent lymphocytic choriomeningitis virus (lcmv) infection, we demonstrate viral targeting of fibroblastic reticular cells (frc) in the lymphoid organs. the frc stromal networks are critical for proper lymphoid architecture and function. high numbers of frc were infected by lcmv clone 13, which causes a chron ... | 2007 | 17878315 |
| normal establishment of virus-specific memory cd8 t cell pool following primary infection during pregnancy. | suppression of cell-mediated immunity has been proposed as a mechanism that promotes maternal tolerance of the fetus but also contributes to increased occurrence and severity of certain infections during pregnancy. despite decades of research examining the effect of pregnancy on ag-specific t cell responses, many questions remain. in particular, quantitative examination of memory cd8 t cell generation following infection during pregnancy remains largely unknown. to examine this issue, we evaluat ... | 2007 | 17878333 |
| differential effect of listeria monocytogenes infection on cytokine production and cytotoxicity of cd8 t cells. | bacterial infection induces a shift to type 1 cd4 t cell subset in an infected host and this shift is important for protection of the host from disease development. many researchers think that the shift is antigen-dependent, but we previously demonstrated an initial induction step for cd4 t cell subsets during listeria monocytogenes (lm) infection is antigen-independent. although listeria is a tlr2 ligand, the immune system of the lm-infected host responded to the pathogen to induce expression o ... | 2007 | 17895607 |
| rt-pcr assay for detection of lassa virus and related old world arenaviruses targeting the l gene. | this study describes an rt-pcr assay targeting the l rna segment of arenaviruses. conserved regions were identified in the polymerase domain of the l gene on the basis of published sequences for lassa virus, lymphocytic choriomeningitis virus (lcmv), pichinde virus and tacaribe virus, as well as 15 novel sequences for lassa virus, lcmv, ippy virus, mobala virus and mopeia virus determined in this study. using these regions as target sites, a pcr assay for detection of all known old world arenavi ... | 2007 | 17905372 |
| discriminating between different pathways of memory cd8+ t cell differentiation. | despite the rapid accumulation of quantitative data on the dynamics of cd8(+) t cell responses following acute viral or bacterial infections of mice, the pathways of differentiation of naive cd8(+) t cells into memory during an immune response remain controversial. currently, three models have been proposed. in the "stem cell-associated differentiation" model, following activation, naive t cells differentiate into stem cell-like memory cells, which then convert into terminally differentiated sho ... | 2007 | 17911585 |
| abrogation of ccl21 chemokine function by transgenic over-expression impairs t cell immunity to local infections. | the cc chemokine receptor 7 (ccr7) and its two ligands, ccl21 and ccl19, play an important role in migration of immune cells to lymphoid tissue. to analyze the function of ccr7 in t cell immunity to infectious agents in vivo, transgenic (tg) mice expressing ccl21 in an ubiquitous fashion were generated. these mice contained high amounts of ccl21 in the serum ( approximately 0.3 microg/ml that resulted in ccr7 down-regulation and in a strongly impaired migration of t cells toward ccl21 in vitro. ... | 2007 | 17914120 |
| quantitative pcr technique for detecting lymphocytic choriomeningitis virus in vivo. | quantitative pcr (qpcr, or real time pcr (rtpcr)) has emerged as a powerful virologic technique for measuring viral replication and viral loads in humans and animal models. we have developed a qpcr assay to accurately quantify lymphocytic choriomeningitis virus (lcmv) in infected mice. we first validated this assay using plasmid dna and lcmv viral stocks. we then demonstrated that the lcmv qpcr assay can detect lcmv in serum and tissues of chronically infected mice (lcmv-clone 13), with greater ... | 2008 | 17920702 |
| 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 |
| lymphocytoid choriomeningitis virus activates plasmacytoid dendritic cells and induces a cytotoxic t-cell response via myd88. | toll-like receptors (tlrs) and retinoic acid-inducible gene i-like helicases (rlhs) are two major machineries recognizing rna virus infection of innate immune cells. intracellular signaling for tlrs and rlhs is mediated by their cytoplasmic adaptors, i.e., myd88 or trif and ips-1, respectively. in the present study, we investigated the contributions of tlrs and rlhs to the cytotoxic t-lymphocyte (ctl) response by using lymphocytoid choriomeningitis virus (lcmv) as a model virus. the generation o ... | 2008 | 17942529 |
| molecular signature of cd8+ t cell exhaustion during chronic viral infection. | chronic viral infections often result in t cell exhaustion. to determine the molecular signature of exhaustion, we compared the gene-expression profiles of dysfunctional lymphocytic choriomeningitis virus (lcmv)-specific cd8(+) t cells from chronic infection to functional lcmv-specific effector and memory cd8(+) t cells generated after acute infection. these data showed that exhausted cd8(+) t cells: (1) overexpressed several inhibitory receptors, including pd-1, (2) had major changes in t cell ... | 2007 | 17950003 |
| defective t helper response of hepatocyte-stimulated cd4 t cells impairs antiviral cd8 response and viral clearance. | in hepatitis, hepatocytes gain the ability to express major histocompatibility complex (mhc) class ii molecules and to present antigen to cd4 t cells. here, we investigated whether mhc class ii-expressing hepatocytes influence in vitro the differentiation of cd4 t cells and in vivo the t-cell response to and control of viral infection. | 2007 | 17967458 |
| type i interferon during viral infections: multiple triggers for a multifunctional mediator. | type i interferons (ifn-i) orchestrate numerous biological and cellular processes and are essential elements during host antiviral defense. after recognition of highly conserved virus signatures, a complex network of signaling events is rapidly initiated and leads to ifn-i synthesis. these cytokines directly induce a strong antiviral state and exert several immune-regulatory actions aimed at preventing virus spread. on the other hand, viruses evolved to evade or subvert the ifn-i system for thei ... | 2007 | 17969455 |
| strength of stimulus and clonal competition impact the rate of memory cd8 t cell differentiation. | the developmental pathways of long-lived memory cd8 t cells and the lineage relationship between memory t cell subsets remain controversial. although some studies indicate the two major memory t cell subsets, central memory t (t(cm)) and effector memory t (t(em)), are related lineages, others suggest that these subsets arise and are maintained independently of one another. in this study, we have investigated this issue and examined the differentiation of memory cd8 t cell subsets by tracking the ... | 2007 | 17982060 |
| extralymphatic virus sanctuaries as a consequence of potent t-cell activation. | t helper cells can support the functions of cd8(+) t cells against persistently infecting viruses such as murine lymphocytic choriomeningitis virus (lcmv), cytomegalovirus, hepatitis c virus and hiv. these viruses often resist complete elimination and remain detectable at sanctuary sites, such as the kidneys and other extralymphatic organs. the mechanisms underlying this persistence are not well understood. here we show that mice with potent virus-specific t-cell responses have reduced levels an ... | 2007 | 17982463 |
| novel plant virus-based vaccine induces protective cytotoxic t-lymphocyte-mediated antiviral immunity through dendritic cell maturation. | currently used vaccines protect mainly through the production of neutralizing antibodies. however, antibodies confer little or no protection for a majority of chronic viral infections that require active involvement of cytotoxic t lymphocytes (ctls). virus-like particles (vlps) have been shown to be efficient inducers of cell-mediated immune responses, but administration of an adjuvant is generally required. we recently reported the generation of a novel vlp system exploiting the self-assembly p ... | 2008 | 17989184 |
| tnf-alpha is critical for antitumor but not antiviral t cell immunity in mice. | tnf-alpha antagonists are widely used in the treatment of inflammatory and autoimmune diseases, but their use is associated with reactivation of latent infections. this highlights the importance of tnf-alpha in immunity to certain pathogens and raises concerns that critical aspects of immune function are impaired in its absence. unfortunately, the role of tnf-alpha in the regulation of t cell responses is clouded by a myriad of contradictory reports. here, we show a role for tnf-alpha and its re ... | 2007 | 17992258 |
| "negative vaccination" by specific cd4 t cell tolerisation enhances virus-specific protective antibody responses. | cooperation of cd4+ t helper cells with specific b cells is crucial for protective vaccination against pathogens by inducing long-lived neutralizing antibody responses. during infection with persistence-prone viruses, prolonged virus replication correlates with low neutralizing antibody responses. we recently described that a viral mutant of lymphocytic choriomeningitis virus (lcmv), which lacks a t helper epitope, counterintuitively induced an enhanced protective antibody response. likewise, pa ... | 2007 | 18000535 |
| normal brain cells contribute to the bystander effect in suicide gene therapy of malignant glioma. | lentiviral vectors pseudotyped with glycoproteins of the lymphocytic choriomeningitis virus (lcmv-gp) are promising candidates for gene therapy of malignant glioma, as they specifically and efficiently transduce glioma cells in vitro and in vivo. here, we evaluated the therapeutic efficacy of lcmv-gp and vesicular stomatitis virus glycoprotein (vsv-g) pseudotyped vectors. | 2007 | 18006778 |
| dna vaccines: a review of developments. | immunisation with purified dna is a powerful technique for inducing immune responses. the concept is very simple, involving insertion of the gene encoding the antigen of choice into a bacterial plasmid, and injection of the plasmid into the host where the antigen is expressed and induces humoral and cellular immunity. this technology can induce immunity to all antigens that can be encoded by dna; this includes all protein, but not carbohydrate, antigens. dna immunisation appears to result in pre ... | 1997 | 18020519 |
| inhibition of cellular entry of lymphocytic choriomeningitis virus by amphipathic dna polymers. | the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) represents a powerful experimental model for the study of the basic virology and pathogenesis of arenaviruses. in the present study, we used the lcmv model to evaluate the anti-viral potential of phosphorothioate oligonucleotides against arenaviruses. our findings indicate that amphipathic dna polymers (aps) are potent inhibitors of infection with a series of lcmv isolates with ic(50) in the low nanomolar range. aps target the s ... | 2008 | 18022208 |
| 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 |
| nonimmunosuppressive chemotherapy: em011-treated mice mount normal t-cell responses to an acute lymphocytic choriomeningitis virus infection. | myelosuppression and associated immunosuppression are major problems in cancer chemotherapy. thus, infection remains a significant source of morbidity and mortality during chemotherapy of cancer patients. viral infections, particularly herpes simplex virus, varicella zoster virus, and cytomegalovirus, result either due to reactivation of latent viruses or new infections as sequelae of chemotherapy and debilitated cell-mediated immunity. ultimately, the resolution of these infections can only be ... | 2007 | 18025274 |
| cellular entry of lymphocytic choriomeningitis virus. | in contrast to most enveloped viruses that enter the host cell via clathrin-dependent endocytosis, the old world arenavirus lymphocytic choriomeningitis virus (lcmv) enters cells via noncoated vesicles that deliver the virus to endosomes, where ph-dependent membrane fusion occurs. here, we investigated the initial steps of lcmv infection. we found that the attachment of lcmv to its cellular receptor alpha-dystroglycan occurs rapidly and is not dependent on membrane cholesterol. however, subseque ... | 2008 | 18045945 |
| [behavior of argentine lymphocytic choriomeningitis virus strains in rodents]. | the activity of lcm virus was first reported in argentina at the beginning of the seventies and only five strains have been isolated from rodents mus domesticus and two from humans. the objective of this paper was to find differential biological characteristics of argentine strains of lcm virus comparing them in relation to the historical strains we and armstrong. regarding the results obtained in tissue culture, when l 929 cells were used, plaque forming units (pfu) were obtained with human and ... | 2007 | 18051229 |
| congenital viral infections of the brain: lessons learned from lymphocytic choriomeningitis virus in the neonatal rat. | the fetal brain is highly vulnerable to teratogens, including many infectious agents. as a consequence of prenatal infection, many children suffer severe and permanent brain injury and dysfunction. because most animal models of congenital brain infection do not strongly mirror human disease, the models are highly limited in their abilities to shed light on the pathogenesis of these diseases. the animal model for congenital lymphocytic choriomeningitis virus (lcmv) infection, however, does not su ... | 2007 | 18052527 |
| systemic and mucosal infection program protective memory cd8 t cells in the vaginal mucosa. | whether mucosal immunization is required for optimal protective cd8 t cell memory at mucosal surfaces is controversial. in this study, using an adoptive transfer system, we compare the efficacy of two routes of acute lymphocytic choriomeningitis viral infection on the generation, maintenance, and localization of ag-specific cd8 t cells in tissues, including the vaginal mucosa. surprisingly, at day 8, i.p. infection results in higher numbers of ag-specific cd8 t cells in the vaginal mucosa and il ... | 2007 | 18056354 |
| analysis of direct and cross-presentation of antigens in tppii knockout mice. | tripeptidyl peptidase ii (tppii) is an oligopeptidase forming giant complexes in the cytosol that have high exo-, but also, endoproteolytic activity. immunohistochemically, the complexes appear as distinct foci in the cytosol. in part controversial biochemical and functional studies have suggested that tppii contributes, on the one hand, positively to ag processing by generating epitope carboxyl termini or by trimming epitope precursors, and, on the other, negatively by destroying potentially an ... | 2007 | 18056356 |
| hematopoiesis and immunity of hoxb4-transduced embryonic stem cell-derived hematopoietic progenitor cells. | the ability of embryonic stem (es) cells to form cells and tissues from all 3 germ layers can be exploited to generate cells that can be used to treat diseases. in particular, successful generation of hematopoietic cells from es cells could provide safer and less immunogenic cells than bone marrow cells, which require severe host preconditioning when transplanted across major histocompatibility complex barriers. here, we exploited the self-renewal properties of ectopically expressed hoxb4, a hom ... | 2008 | 18056836 |
| revisiting estimates of ctl killing rates in vivo. | recent experimental advances have allowed the estimation of the in vivo rates of killing of infected target cells by cytotoxic t lymphocytes (ctl). we present several refinements to a method applied previously to quantify killing of targets in the spleen using a dynamical model. we reanalyse data previously used to estimate killing rates of ctl specific for two epitopes of lymphocytic choriomeningitis virus (lcmv) in mice and show that, contrary to previous estimates the "killing rate" of effect ... | 2007 | 18074025 |
| efficient induction of mucosal and systemic immune responses by virus-like particles administered intranasally: implications for vaccine design. | intranasal (i.n.) immunization aims to induce local as well as systemic immune responses. in the present study, we assessed a vaccine platform based on virus-like particles (vlp) derived from the rna phage qbeta for i.n. immunization. we found that both i.n. and subcutaneous (s.c.) administration of qbeta-vlp elicited strong and comparable specific igg responses in serum and lung. surprisingly, both routes also induced high levels of specific iga in serum. in contrast, only i.n. administration o ... | 2008 | 18081037 |
| 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 |
| myositis in mice following intramuscular injection of viruses of the mouse encephalomyelitis group and of certain other neurotropic viruses. | a study has been made of the local effects following intramuscular injection of various neurotropic viruses. early massive necrosis of muscle fibers accompanied by edema and acute inflammatory reaction is produced by jungeblut's sk virus even in low concentrations. similar but more slowly developing lesions follow the introduction of mouse encephalomyelitis gd-vii and fa strains. strain 4727 (to type) produces inflammatory changes with fibrosis in the intermuscular septa and necrosis of scattere ... | 1949 | 18099166 |
| cross-priming of a single viral protein from lymphocytic choriomeningitis virus alters immunodominance hierarchies of cd8+ t cells during subsequent viral infections. | immunogenic epitopes that stimulate cd8+ t cells can be organized into an immunodominance hierarchy, based on their ability to induce t-cell priming and subsequent expansion. cytotoxic cd8+ t cells can be primed through the cross-priming pathway, where exogenous viral proteins are acquired by professional antigen-presenting cells (papcs). we have previously reported that lymphocytic choriomeningitis nucleoprotein (lcmv-np) expressed in hek cells (hek-np) induces cross-priming of cd8+ t cells in ... | 2007 | 18158732 |
| 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 |