| dissection of antiviral and immune regulatory functions of tumor necrosis factor receptors in a chronic lymphocytic choriomeningitis virus infection. | the effector function of cd8 t cells is mediated via cell-mediated cytotoxicity and production of cytokines like gamma interferon (ifn-gamma) and tumor necrosis factor alpha (tnf-alpha). while the roles of perforin-dependent cytotoxicity, ifn-gamma, and tnf-alpha in controlling acute viral infections are well studied, their relative importance in defense against chronic viral infections is not well understood. using mice deficient for tnf receptor (tnfr) i and/or ii, we show that tnf-tnfr intera ... | 2004 | 15047807 |
| immediate cytotoxicity but not degranulation distinguishes effector and memory subsets of cd8+ t cells. | cd8+ t cells play a central role in the resolution and containment of viral infections. a key effector function of cd8+ t cells is their cytolytic activity toward infected cells. here, we studied the regulation of cytolytic activity in naive, effector, and central versus effector memory cd8+ t cells specific for the same glycoprotein-derived epitope of lymphocytic choriomeningitis virus. our results show that the kinetics of degranulation, assessed by a novel flow cytometric based assay, were id ... | 2004 | 15051762 |
| complexity of cnc transcription factors as revealed by gene targeting of the nrf3 locus. | cap'n'collar (cnc) family basic leucine zipper transcription factors play crucial roles in the regulation of mammalian gene expression and development. to determine the in vivo function of the cnc protein nrf3 (nf-e2-related factor 3), we generated mice deficient in this transcription factor. we performed targeted disruption of two nrf3 exons coding for cnc homology, basic dna-binding, and leucine zipper dimerization domains. nrf3 null mice developed normally and revealed no obvious phenotypic d ... | 2004 | 15060151 |
| an animal model of hemophagocytic lymphohistiocytosis (hlh): cd8+ t cells and interferon gamma are essential for the disorder. | hemophagocytic lymphohistiocytosis (hlh) is a rare disorder with familial and acquired forms. the familial form is associated with mutations in the perforin gene and both forms are associated with severe defects in lymphocyte cytotoxic function. we examined perforin-deficient mice as a model of hlh in order to gain insight into this poorly understood disorder. while these mice do not spontaneously develop hlh-like symptoms, we found that they manifest all of the features of hlh after infection w ... | 2004 | 15069016 |
| do thymically and strictly extrathymically developing t cells generate similar immune responses? | if present in sufficient numbers, could extrathymic t cells substitute for thymus-derived t cells? to address this issue, we studied extrathymic t cells that develop in athymic mice under the influence of oncostatin m (om). in this model, extensive t-cell development is probably due to amplification of a minor pathway of t-cell differentiation taking place only in the lymph nodes. extrathymic cd4 t cells expanded poorly and were deficient in providing b-cell help after infection with vesicular s ... | 2004 | 15070691 |
| a stochastic model of cytotoxic t cell responses. | we have constructed a stochastic stage-structured model of the cytotoxic t lymphocyte (ctl) response to antigen and the maintenance of immunological memory. the model follows the dynamics of a viral infection and the stimulation, proliferation, and differentiation of naïve cd8(+) t cells into effector ctl, which can eliminate virally infected cells. the model is capable of following the dynamics of multiple t cell clones, each with a t cell receptor represented by a digit string. mhc-viral pepti ... | 2004 | 15094017 |
| t-bet controls autoaggressive cd8 lymphocyte responses in type 1 diabetes. | the t-box transcription factor t-bet is known to control lineage commitment and interferon-gamma production by t helper 1 (th1) cd4 lymphocytes. we report here that t-bet is essential for development of cd8 lymphocyte-dependent autoimmune diabetes (type 1 diabetes [t1d]) in the rat insulin promoter-lymphocytic choriomeningitis virus (lcmv) transgenic model for virally induced t1d. in the absence of t-bet, autoaggressive (anti-lcmv) cd8 lymphocytes were reduced in number and produced less ifn-gam ... | 2004 | 15096540 |
| determination of structural principles underlying three different modes of lymphocytic choriomeningitis virus escape from ctl recognition. | lymphocytic choriomeningitis virus infection of h-2(b) mice generates a strong cd8(+) ctl response mainly directed toward three immunodominant epitopes, one of which, gp33, is presented by both h-2d(b) and h-2k(b) mhc class i molecules. this ctl response acts as a selective agent for the emergence of viral escape variants. these variants generate altered peptide ligands (apls) that, when presented by class i mhc molecules, antagonize ctl recognition and ultimately allow the virus to evade the ce ... | 2004 | 15100292 |
| immunology. cd8alphaalpha and t cell memory. | | 2004 | 15105485 |
| cd8alphaalpha-mediated survival and differentiation of cd8 memory t cell precursors. | memory t cells are long-lived antigen-experienced t cells that are generally accepted to be direct descendants of proliferating primary effector cells. however, the factors that permit selective survival of these t cells are not well established. we show that homodimeric alpha chains of the cd8 molecule (cd8alphaalpha) are transiently induced on a selected subset of cd8alphabeta+ t cells upon antigenic stimulation. these cd8alphaalpha molecules promote the survival and differentiation of activat ... | 2004 | 15105501 |
| suppressing the suppressors. | | 2004 | 15109942 |
| does toll-like receptor 3 play a biological role in virus infections? | the toll-like receptor (tlr) family functions to recognize conserved microbial and viral structures with the purpose of activating signal pathways to instigate immune responses against infections by these organisms. for example, in vitro studies reveal that the tlr3 ligand is a double-stranded rna (dsrna), a product of viral infections. from this observation, it has been proposed that tlr3 is likely an important first signal for virus infections. we approached this issue by investigating the rol ... | 2004 | 15110521 |
| loading of mhc class i and ii presentation pathways by exogenous antigens: a quantitative in vivo comparison. | the mhc class i pathway is usually fueled by endogenous ags, while exogenous ags reach the mhc class ii pathway. although exogenous epitopes may also enter the mhc class i pathway, quantification of the efficiency of the process has remained a difficult task. in an attempt of such a quantification, we directly compared the amount of exogenous virus-like particles required for induction of cytotoxic t cell responses by cross-priming with the amount of virus-like particles required for induction o ... | 2004 | 15128799 |
| visualizing the viral burden: phenotypic and functional alterations of t cells and apcs during persistent infection. | persistent viral infections continue to present major public health problems. failure to achieve virus control confronts the immune system with a chronic viral burden that may involve immune cells themselves and directly compromise the functionality of effector lymphocytes and apcs. in this study we use the lymphocytic choriomeningitis virus system for persistent viral infection of its natural murine host and use analytical techniques for direct ex vivo visualization of virus-infected immune cel ... | 2004 | 15128812 |
| viral flip impairs survival of activated t cells and generation of cd8+ t cell memory. | viral flips (vflips) interfere with apoptosis signaling by death-domain-containing receptors in the tnfr superfamily (death receptors). in this study, we show that t cell-specific transgenic expression of mc159-vflip from the human molluscum contagiosum virus blocks cd95-induced apoptosis in thymocytes and peripheral t cells, but also impairs postactivation survival of in vitro activated primary t cells despite normal early activation parameters. mc159 vflip impairs t cell development to a lesse ... | 2004 | 15128821 |
| efficient t-cell surveillance of the cns requires expression of the cxc chemokine receptor 3. | t-cells play an important role in controlling viral infections inside the cns. to study the role of the chemokine receptor cxcr3 in the migration and positioning of virus-specific effector t-cells within the brain, cxcr3-deficient mice were infected intracerebrally with lymphocytic choriomeningitis virus (lcmv). analysis of the induction phase of the antiviral cd8+ t-cell response did not reveal any immune defects in cxcr3-deficient mice. yet, when mice were challenged with lcmv intracerebrally, ... | 2004 | 15152045 |
| cytokine production by virus-specific cd8(+) t cells varies with activation state and localization, but not with tcr avidity. | the ability of virus-specific cd8(+) t cells to produce cytokines was studied in mice infected with lymphocytic choriomeningitis virus and vesicular stomatitis virus. intracellular staining was used to visualize cytokine-producing cd8(+) and cd4(+) t cells. overall, virus-specific cd8(+) t cells produce a similar range of cytokines (ifn-gamma, tnf-alpha, il-2, gm-csf, rantes, mip-1alpha and mip-1beta) as cd4(+) t cells, but the relative distribution of cytokine-producing subsets is different. mo ... | 2004 | 15166455 |
| anti-cd137 antibodies in the treatment of autoimmune disease and cancer. | cd137 (4-1bb), is an inducible t-cell costimulatory receptor and a member of the tumor necrosis factor receptor (tnfr) superfamily. it is expressed on activated t cells and activated natural killer (nk) cells, but is constitutively expressed on a population of splenic dendritic cells (dcs). the natural counter receptor for cd137 is 4-1bb ligand, a member of the tnf superfamily that is weakly expressed on naïve or resting b cells, macrophages, and dcs. upon activation, the level of 4-1bbl express ... | 2004 | 15181282 |
| role of cell cycle regulator e2f1 in regulating cd8 t cell responses during acute and chronic viral infection. | to determine the role of cell cycle regulatory protein e2f1 in t cell immunity, we compared antigen-specific cd8 t cell responses between wild type (+/+) and e2f1-deficient (e2f1-/-) mice following an acute and chronic infection with lymphocytic choriomeningitis virus (lcmv). during an acute lcmv infection, although lcmv-specific effector cd8 t cells from e2f1-/- mice were less susceptible to activation-induced cell death (aicd) in vitro, e2f1 deficiency had no significant effect on the: (1) exp ... | 2004 | 15207641 |
| origin and fate of lymphocytic choriomeningitis virus-specific cd8+ t cells coexpressing the inhibitory nk cell receptor ly49g2. | cd8+ t cells that coexpress the inhibitory nk cell receptor, ly49g2 (g2), are present in immunologically naive c57bl/6 mice but display ags found on memory t cells. to assess how g2+cd8+ cells relate to bona fide memory cells, we examined the origin and fate of lymphocytic choriomeningitis virus (lcmv)-induced g2+cd8+ cells. during early (day 4) acute lcmv infection, both g2+ and g2-cd8+ t cell subsets underwent an attrition in number and displayed an activation (cd69(high)1b11(high)cd62l(low)) ... | 2004 | 15210808 |
| lentiviral transduction of dendritic cells confers protective antiviral immunity in vivo. | control of a viral infection in vivo requires a rapid and efficient cytotoxic-t-lymphocyte response. we demonstrate that lentivirus-mediated introduction of antigen in dendritic cells confers a protective antiviral immunity in vivo in a lymphocytic choriomeningitis virus model. therefore, lentiviral vectors may be excellent vaccine candidates for viral infections. | 2004 | 15220461 |
| peptide variants of viral ctl epitopes mediate positive selection and emigration of ag-specific thymocytes in vivo. | during development, thymocytes carrying tcrs mediating low-affinity interactions with mhc-bound self-peptides are positively selected for export into the mature peripheral t lymphocyte pool. thus, exogenous administration of certain altered peptide ligands (apl) with reduced tcr affinity relative to cognate ags may provide a tool to elicit maturation of desired tcr specificities. to test this "thymic vaccination" concept, we designed apl of the viral ctl epitopes gp33-41 and vesicular stomatitis ... | 2004 | 15240703 |
| electron microscopy of an alpha-dystroglycan fragment containing receptor sites for lymphocytic choriomeningitis virus and laminin, and use of the receptoid body as a reagent to neutralize virus. | we report the electron microscopic structure of an alpha-dystroglycan (alpha-dg) fragment (dgekfc4) that contains binding sites for lymphocytic choriomeningitis virus (lcmv) and the extracellular matrix (ecm) molecule laminin. in electron microscopic images, dgekfc4 appears as dumbbell-shaped rods with a length of 7.5 +/- 0.5 nm and width of 3 +/- 0.3 nm. the c-terminal human fc allows binding of anti-human fc antibody resulting in formation of immune complexes that preserve alpha-dg binding to ... | 2004 | 15246261 |
| use of alternative receptors different than alpha-dystroglycan by selected isolates of lymphocytic choriomeningitis virus. | long-term infections with viruses permit the generation of variants that evolve specific growth advantages in certain tissues and may show altered disease potentials. the selection of such variants is influenced by the host tissue and often involves virus-receptor interactions. here we report studies of receptor usage by several lymphocytic choriomeningitis virus (lcmv) isolates that expressed different disease patterns. consistent with our previous studies, we found that, with one exception, mu ... | 2004 | 15246281 |
| urolithiasis associated with experimental lymphocytic choriomeningitis virus inoculation in lewis rats. | a high frequency of struvite urolithiasis, hydronephrosis, and other urinary tract lesions developed in a group of lewis rats inoculated intracranially with lymphocytic choriomeningitis virus (lcmv). initially, clinically ill rats were referred to necropsy: 30 rats over 3 years. these rats had high frequency of urolithiasis (8/30, 27%), hydronephrosis (12/30, 40%), cystitis (9/30, 30%), transitional cell carcinoma (4/30, 13%), and pyelonephritis (19/30, 63%). lesions were more common in lcmv-ino ... | 2004 | 15253279 |
| neutrophil involvement in cross-priming cd8+ t cell responses to bacterial antigens. | substantial cd8(+) t cell responses are generated after infection of mice with recombinant listeria monocytogenes strains expressing a model epitope (lymphocytic choriomeningitis virus np(118-126)) in secreted and nonsecreted forms. l. monocytogenes gains access to the cytosol of infected cells, where secreted ags can be accessed by the endogenous mhc class i presentation pathway. however, the route of presentation of the nonsecreted ag in vivo remains undefined. in this study we show that neutr ... | 2004 | 15265934 |
| cutting edge: distinct roles for t help and cd40/cd40 ligand in regulating differentiation of proliferation-competent memory cd8+ t cells. | murine primary antiviral cytotoxic t cell (ctl) responses are often induced in the absence of th cells. in this study, we show that virus-like particles, if combined with dna rich in cpg motifs, efficiently trigger primary ctl responses and comparable frequencies of memory ctls in the presence or absence of t help. however, memory ctls primed in the absence of t help failed to proliferate upon viral challenge. nevertheless, they were efficiently recruited to sites of inflammation, indicating tha ... | 2004 | 15294930 |
| functional characterization of mhc class ii-restricted cd8+cd4- and cd8-cd4- t cell responses to infection in cd4-/- mice. | classical cd4(+) and cd8(+) t cells recognize ag presented by mhc class ii (mhcii) and mhc class i (mhci), respectively. however, our results show that cd4(-/-) mice mount a strong, readily detectable cd8(+) t cell response to mhcii-restricted epitopes after a primary bacterial or viral infection. these mhcii-restricted cd8(+)cd4(-) t cells are more similar to classical cd8(+) t cells than to cd4(+) t cells in their expression of effector functions during a primary infection, yet they also diffe ... | 2004 | 15294964 |
| partial activation of neonatal cd11c+ dendritic cells and induction of adult-like cd8+ cytotoxic t cell responses by synthetic microspheres. | neonatal cytotoxic t cell responses have only been elicited to date with immunogens or delivery systems inducing potent direct apc activation. to define the minimal activation requirements for the induction of neonatal cd8(+) cytotoxic responses, we used synthetic microspheres (ms) coated with a single cd8(+) t cell peptide from lymphocytic choriomeningitis virus (lcmv) or hiv-1. unexpectedly, a single injection of peptide-conjugated ms without added adjuvant induced cd4-dependent ag-specific ne ... | 2004 | 15294984 |
| oral administration with papillomavirus pseudovirus encoding il-2 fully restores mucosal and systemic immune responses to vaccinations in aged mice. | infectious diseases are one of the major threats for the elderly because their immune system is often compromised, and vaccinations to prevent these infections are not effective. a major defect in their immune system seems to be the inability of t cells to produce il-2. we used papillomavirus (pv) pseudoviruses (psvs) as a model vaccine and a gene delivery vector to address how to enhance immune responses to vaccinations. we found that oral immunization with pv psv induced minimal mucosal and sy ... | 2004 | 15294987 |
| deliberate removal of t cell help improves virus-neutralizing antibody production. | the b cell response to lymphocytic choriomeningitis virus is characterized by a cd4(+) t cell-dependent polyclonal hypergammaglobulinemia and delayed formation of virus-specific neutralizing antibodies. here we provide evidence that, paradoxically, because of polyclonal b cell activation, virus-specific t cell help impairs the induction of neutralizing antibody responses. experimental reduction in cd4(+) t cell help in vivo resulted in potent neutralizing antibody responses without impairment of ... | 2004 | 15300247 |
| cd4+ t cells are required for the maintenance, not programming, of memory cd8+ t cells after acute infection. | immunization in the absence of cd4(+) t cell help results in defective cd8(+) t cell memory, deficient recall responses and diminished protective immunity. here we investigated at what stage during the immune response to pathogen cd4(+) t cells are essential in the promotion of functional cd8(+) t cell memory. memory cd8(+) t cell numbers decreased gradually in the absence of cd4(+) t cells despite the presence of similar numbers of memory cell precursors at the peak of the effector phase. adopt ... | 2004 | 15300249 |
| altered cd45 isoform expression affects lymphocyte function in cd45 tg mice. | transgenic mice have been constructed expressing high (cd45rabc) and low (cd45r0) molecular weight cd45 isoforms on a cd45-/- background. phenotypic analysis and in vivo challenge of these mice with influenza and lymphocytic choriomeningitis viruses shows that t cell differentiation and peripheral t cell function are related to the level of cd45 expression but not to which cd45 isoform is expressed. in contrast, b cell differentiation is not restored, irrespective of the level of expression of a ... | 2004 | 15302847 |
| regulation of innate and adaptive immune responses by map kinase phosphatase 5. | mitogen-activated protein (map) kinases are essential regulators in immune responses, and their activities are modulated by kinases and phosphatases. map kinase phosphatase (mkp) is a family of dual-specificity phosphatases whose function is evolutionarily conserved. a number of mammalian mkps have been identified so far, but their specific physiological functions in negative regulation of map kinases have not been genetically defined. here we examine innate and adaptive immune responses in the ... | 2004 | 15306813 |
| serine protease inhibitor 2a is a protective factor for memory t cell development. | an essential event in the development of memory cd8(+) t lymphocytes is the escape of progenitors from programmed cell death, but how this is mediated is unclear. here we report that the gene encoding serine protease inhibitor 2a (spi2a), an inhibitor of lysosomal executioner proteases dependent on transcription factor nf-kappab, is upregulated in memory cell precursors. spi2a upregulation protected lymphocytic choriomeningitis virus-specific memory progenitors from programmed cell death. thus, ... | 2004 | 15311278 |
| constitutive expression of ccr7 directs effector cd8 t cells into the splenic white pulp and impairs functional activity. | antigenic stimulation down-regulates ccr7 on effector t cells. to analyze the importance of ccr7 down-regulation, transgenic (tg) mice constitutively expressing ccr7 were generated. cd8 t cells with defined ag specificity were obtained by breeding ccr7-tg mice with p14 tcr-tg mice specific for lymphocytic choriomeningitis virus. transgenic ccr7 expression did not impair proliferation of p14.ccr7 t cells induced by lymphocytic choriomeningitis virus infection, but prevented ccr7 down-regulation. ... | 2004 | 15322160 |
| lcmv-mediated hepatitis in rhesus macaques: we but not arm strain activates hepatocytes and induces liver regeneration. | lymphocytic chorimeningitis virus (lcmv), the prototype arenavirus, and lassa virus (lasv), causative agent of lassa hemorrhagic fever (lhf), belong to the old world group of the family arenaviridae. both viruses have extensive strain diversity and significant variations in lethality and pathogenicity for man and experimental animals. we have shown that the lhf-like infection of rhesus macaques with the we strain of lcmv affects liver functions, induces hepatocyte proliferation, and causes a ris ... | 2004 | 15338320 |
| molecular characterization of virus-induced autoantibody responses. | here we present a comprehensive molecular mapping of virus-induced autoimmune b cell responses obtained by serological identification of antigens by recombinant expression cloning analysis. immunoscreening of cdna expression libraries of various organs (lung, liver, and spleen) using sera from mice infected with cytopathic (vaccinia virus [vv]) or noncytopathic (lymphocytic choriomeningitis virus [lcmv]) viruses revealed a broad specificity of the elicited autoantibody response. interestingly, t ... | 2004 | 15353556 |
| a role for the granzyme b inhibitor serine protease inhibitor 6 in cd8+ memory cell homeostasis. | generation and maintenance of protective immunological memory is the goal of vaccination programs. it has recently become clear that cd8+ memory t cells are derived directly from ctls. the mechanisms underlying this transformation and the subsequent survival of memory cells are not completely understood. however, some effector molecules required by ctls to eliminate infected cells have also been shown to control the number of ag-specific cells. we report that memory cells express high levels of ... | 2004 | 15356127 |
| cd8 t cell responses to lymphocytic choriomeningitis virus in early growth response gene 1-deficient mice. | previous in vitro work has implicated a role for transcriptional factor early growth response gene 1 (egr1) in regulating immune responses. however, the in vivo role of egr1 in orchestrating t cell responses has not been studied. to investigate the importance of egr1 in t cell immunity, we compared ag-specific cd8 t cell responses between wild type (+/+) and egr1-deficient (egr1-/-) mice following an acute infection with lymphocytic choriomeningitis virus (lcmv). these studies revealed that the ... | 2004 | 15356133 |
| immunoproteasomes down-regulate presentation of a subdominant t cell epitope from lymphocytic choriomeningitis virus. | the cytotoxic t cell response to pathogens is usually directed against a few immunodominant epitopes, while other potential epitopes are either subdominant or not used at all. in c57bl/6 mice, the acute cytotoxic t cell response against lymphocytic choriomeningitis virus is directed against immunodominant epitopes derived from the glycoprotein (gp33-41) and the nucleoprotein (np396-404), while the gp276-286 epitope remains subdominant. despite extensive investigations, the reason for this hierar ... | 2004 | 15356141 |
| public, private and non-specific antibodies induced by non-cytopathic viral infections. | lymphocytic choriomeningitis virus (lcmv) represents a useful experimental model of murine infection with a non-cytopathic virus, bearing resemblance to hiv and hepatitis c virus (hcv) infections in humans. recent data from the lcmv model indicate that the humoral immune response that is induced by non-cytopathic viruses is far more complex than previously appreciated. lcmv-induced igg production is largely polyclonal, with more than 90% of the antibody repertoire constituting non-relevant speci ... | 2004 | 15358263 |
| reduced antigen concentration and costimulatory blockade increase ifn-gamma secretion in naive cd8+ t cells. | cd8+ t cells are killer cells but also major producers of ifn-gamma. we have investigated the effects of peptide antigen titration and costimulatory blockade on ifn-gamma production and proliferation by naive cd8+ t cells. mature dendritic cells (dc) pulsed with high amounts of agonist peptide triggered proliferation but little ifn-gamma secretion in individual t cells. in contrast, immature dc pulsed with similar amounts of peptide induced ifn-gamma secretion in a larger fraction of t cells but ... | 2004 | 15384046 |
| active immunization of mice with ultraviolet-inactivated lymphocytic choriomeningitis virus vaccine and results of immune serum therapy. | | 1949 | 15392986 |
| multiplication of certain neurotropic viruses in the rabbit eye following intraocular inoculation. | lymphocytic choriomeningitis virus and semliki forest virus readily multiply in the rabbit eye following inoculation into the vitreous. less than 10 mouse ld(50) of lcm virus was sufficient to induce multiplication in the eye, whereas, approximately 1000 ld(50) of sfv was required to initiate infection. both viruses multiplied in the rabbit eye as an inapparent infection. little or no virus could be recovered from the optic nerves or brains of the rabbits, although virus was present in high tite ... | 1950 | 15395572 |
| suppression of viral specific primary t-cell response following intense physical exercise in young but not old mice. | intense exercise to exhaustion leads to increased susceptibility and severity of infections. t cells play an essential role in control of viral infections. whereas immune suppression is considered as a likely mechanism for exhaustive exercise-induced susceptibility to infection, we know little about viral-specific t-cell response following exhaustive exercise in young or old mice. in this study, one group of female young (10-12 wk) and old (22-24 mo) c57bl/6 mice was exposed to a single bout of ... | 2005 | 15448122 |
| gene-gun dna vaccination aggravates respiratory syncytial virus-induced pneumonitis. | a cd8+ t-cell memory response to respiratory syncytial virus (rsv) was generated by using a dna vaccine construct encoding the dominant kd-restricted epitope from the viral transcription anti-terminator protein m2 (m2(82-90)), linked covalently to human beta2-microglobulin (beta2m). cutaneous gene-gun immunization of balb/c mice with this construct induced an antigen-specific cd8+ t-cell memory. after intranasal rsv challenge, accelerated cd8+ t-cell responses were observed in pulmonary lymph no ... | 2004 | 15448365 |
| enhanced expression of cell cycle regulatory genes in virus-specific memory cd8+ t cells. | unlike naive cd8+ t cells, antigen-experienced memory cd8+ t cells persist over time due to their unique ability to homeostatically proliferate. it was hypothesized that memory cells might differentially regulate the expression of genes that control the cell cycle to facilitate homeostatic proliferation. to test this, the expression levels of 96 different cell cycle regulatory genes were compared between transgenic naive and memory cd8+ t cells that specifically recognize the gp33-41 epitope of ... | 2004 | 15452215 |
| antioxidant treatment reduces expansion and contraction of antigen-specific cd8+ t cells during primary but not secondary viral infection. | during many viral infections, antigen-specific cd8(+) t cells undergo large-scale expansion. after viral clearance, the vast majority of effector cd8(+) t cells undergo apoptosis. previous studies have implicated reactive oxygen intermediates (roi) in lymphocyte apoptosis. the purpose of the experiments presented here was to determine the role of roi in the expansion and contraction of cd8(+) t cells in vivo during a physiological response such as viral infection. mice were infected with lymphoc ... | 2004 | 15452243 |
| myristoylation of the ring finger z protein is essential for arenavirus budding. | the arenavirus small ring finger z protein is the main driving force of arenavirus budding. the primary structure of z is devoid of hydrophobic transmembrane domains, but both lymphocytic choriomeningitis virus (lcmv) and lassa fever virus z proteins accumulate near the inner surface of the plasma membrane and are strongly membrane associated. all known arenavirus z proteins contain a glycine (g) at position 2, which is a potential acceptor site for a myristoyl moiety. metabolic labeling showed ... | 2004 | 15452271 |
| tcr affinity and negative regulation limit autoimmunity. | autoimmune diseases are often mediated by self-reactive t cells, which must be activated to cause immunopathology. one mechanism, known as molecular mimicry, proposes that self-reactive t cells may be activated by pathogens expressing crossreactive ligands. here we have developed a model to investigate how the affinity of the t-cell receptor (tcr) for the activating agent influences autoimmunity. our model shows that an approximately fivefold difference in the tcr affinity for the activating lig ... | 2004 | 15467726 |
| kinetics of protective antibodies are determined by the viral surface antigen. | delayed and weak virus neutralizing antibody (nab) responses represent a hallmark correlating not only with the establishment of persistent infection but also with unsuccessful vaccine development. using a reverse genetic approach, we evaluated possible underlying mechanisms in 2 widely studied viral infection models. swapping the glycoproteins (gps) of lymphocytic choriomeningitis virus (lcmv, naturally persisting, noncytolytic, inefficient nab inducer) and vesicular stomatitis virus (vsv, nonp ... | 2004 | 15467838 |
| rebuilding an immune-mediated central nervous system disease: weighing the pathogenicity of antigen-specific versus bystander t cells. | although both self- and pathogen-specific t cells can participate in tissue destruction, recent studies have proposed that after viral infection, bystander t cells of an irrelevant specificity can bypass peptide-mhc restriction and contribute to undesired immunopathological consequences. to evaluate the importance of this mechanism of immunopathogenesis, we determined the relative contributions of ag-specific and bystander cd8+ t cells to the development of cns disease. using lymphocytic choriom ... | 2004 | 15470017 |
| preapoptotic phenotype of viral epitope-specific cd8 t cells precludes memory development and is an intrinsic property of the epitope. | virus-specific cd8 t cells after clearance of infection reduce their number in lymphoid organs by apoptotic death and by migration into peripheral tissues. during and after infection, many lymphocytic choriomeningitis virus (lcmv)-specific cd8 t cells in lymphoid but not peripheral tissues are in a preapoptotic state, as detected by the early apoptosis marker annexin v. in this report, we investigated the significance of this preapoptotic state and how it may be influenced by viral epitope speci ... | 2004 | 15470058 |
| [screening for antibodies against zoonotic agents among employees of the zoological garden of vienna, schönbrunn, austria]. | the aim of this study was to investigate the prevalence of antibodies against zoonotic agents in employees of the zoological garden of vienna, schönbrunn, austria. sixty out of 120 employees participated in the study. in 97% of them antibodies to at least one zoonotic agent were identified. only two participants were free of antibodies to the zoonotic agents tested. the following seroprevalences (in brackets) were obtained: viral zoonotic (and potentially zoonotic) agents: influenzavirus a/h1n1 ... | 2004 | 15495931 |
| antigen-independent memory cd8 t cells do not develop during chronic viral infection. | memory t cells can persist for extended periods in the absence of antigen, and long-term t cell immunity is often seen after acute infections. paradoxically, there have been observations suggesting that t cell memory may be antigen-dependent during chronic infections. to elucidate the underlying mechanisms we have compared memory cd8 t cell differentiation during an acute versus chronic infection by using the mouse model of infection with lymphocytic choriomeningitis virus. we found that during ... | 2004 | 15505208 |
| perforin and fas act together in the induction of apoptosis, and both are critical in the clearance of lymphocytic choriomeningitis virus infection. | in this report we questioned the current view that the two principal cytotoxic pathways, the exocytosis and the fas ligand (fasl)/fas-mediated pathway, have largely nonoverlapping biological roles. for this purpose we have analyzed the response of mice that lack fas as well as granzyme a (gzma) and gzmb (fasxgzmaxb(-/-)) to infection with lymphocytic choriomeningitis virus (lcmv). we show that fasxgzmaxb(-/-) mice, in contrast to b6, fas(-/-), and gzmaxb(-/-) mice, do not recover from a primary ... | 2004 | 15507626 |
| single-epitope dna vaccination prevents exhaustion and facilitates a broad antiviral cd8+ t cell response during chronic viral infection. | induction of a monospecific antiviral cd8+ t cell response may pose a risk to the host due to the narrow t cell response induced. at the individual level, this may result in selection of cd8+ t cell escape variants, particularly during chronic viral infection. second, prior immunization toward a single dominant epitope may suppress the response to other viral epitopes, and this may lead to increased susceptibility to reinfection with escape variants circulating in the host population. to address ... | 2004 | 15528367 |
| bone marrow plasmacytoid dendritic cells can differentiate into myeloid dendritic cells upon virus infection. | two subsets of dendritic cell (dcs), plasmacytoid (p) and myeloid (m) dcs, have been described in humans and mice. these subsets are known to have divergent roles during an immune response, but their developmental course is unclear. here we report that virus infection induces bone marrow pdcs to differentiate into mdcs, thereby undergoing profound phenotypic and functional changes including the acquisition of enhanced antigen-presenting capacity and the ability to recognize different microbial s ... | 2004 | 15531885 |
| role of isg15 protease ubp43 (usp18) in innate immunity to viral infection. | innate immune responses provide the host with an early protection barrier against infectious agents, including viruses, and help shape the nature and quality of the subsequent adaptive immune responses of the host. expression of isg15 (ucrp), a ubiquitin-like protein, and protein isgylation are highly increased upon viral infection. we have identified ubp43 (usp18) as an isg15 deconjugating protease. protein isgylation is enhanced in cells deficient in ubp43 (ref. 6). here we have examined the r ... | 2004 | 15531891 |
| optimized large-scale production of high titer lentivirus vector pseudotypes. | the goal of the present study was to develop an efficient transient transfection method for large-scale production of high titer lentivirus vector stocks of eight different pseudotypes. the envelope genes used for this purpose were those from vsv-g, mokola, rabies, mlv-ampho, mlv-10a1, lcmv-we, and lcmv-arm53b. all envelopes were cloned into phcmv, which yielded lentivirus vector titers one, two, or three orders of magnitude higher than the original plasmids for the rabies, mlv-10a1, and mlv-amp ... | 2004 | 15542136 |
| reduction in cd1d expression on dendritic cells and macrophages by an acute virus infection. | mice were infected with lymphocytic choriomeningitis virus (lcmv) to determine if changes in cd1d expression occurred during an acute virus infection. it is interesting that a decrease in cd1d expression on splenic dendritic cells (dc) and macrophages (mphi) was observed for at least 3 months post-lcmv infection, and vaccinia virus and vesicular stomatitis virus induced similar changes in cd1d upon infection with those viruses. the reduction of cd1d cell-surface expression on dc and mphi was ind ... | 2005 | 15548574 |
| the contraction phase of virus-specific cd8+ t cells is unaffected by a pan-caspase inhibitor. | the effectiveness of protection conferred by cd8(+) memory t cells is determined by both their quality and their quantity, which suggests that vaccine efficacy might be improved if it were possible to increase the size of the memory pool. approximately 90% of virus-specific cd8(+) t cells die during the contraction phase and, herein, we have attempted to increase the memory pool by reducing cd8(+) t cell death. cd8(+) t cell contraction has been attributed to apoptosis, or programmed cell death ... | 2004 | 15557151 |
| impact of ccr7 on priming and distribution of antiviral effector and memory ctl. | the chemokine receptor ccr7 is a key factor in the coordinate migration of t cells and dendritic cells (dc) into and their localization within secondary lymphoid organs. in this study we investigated the impact of ccr7 on cd8(+) t cell responses by infecting ccr7(-/-) mice with lymphocytic choriomeningitis virus (lcmv). we found that the absence of ccr7 affects the magnitude of an antiviral ctl response during the acute phase, with reduced numbers of virus-specific ctl in all lymphoid and nonlym ... | 2004 | 15557160 |
| activation of virus-specific cd8+ t cells by lipopolysaccharide-induced il-12 and il-18. | virus-specific t cells represent a hallmark of ag-specific, adaptive immunity. however, some t cells also demonstrate innate functions, including non-ag-specific ifn-gamma production in response to microbial products such as lps or exposure to il-12 and/or il-18. in these studies we examined lps-induced cytokine responses of cd8(+) t cells directly ex vivo. following acute viral infection, 70-80% of virus-specific t cells will produce ifn-gamma after exposure to lps-induced cytokines, and neutra ... | 2004 | 15557182 |
| small mammal virology. | most viral infections in small mammals are transient and rarely produce clinical signs. when clinical signs do appear, they are often of a multifactorial etiology such as respiratory infection with sendai virus and the bacteria m. pulmonis in rodents. diagnosis is generally made based on clinical signs, while therapy involves treatment for concurrent bacterial infections and supportive care. small mammals may carry zoonotic viruses such as lcmv, but natural infections are uncommon. viral disease ... | 2005 | 15585191 |
| new approaches to eliciting protective immunity through t cell repertoire manipulation: the concept of thymic vaccination. | conventional vaccines afford protection against infectious diseases by expanding existing pathogen-specific peripheral lymphocytes, both cd8 cytotoxic effector (ctl) and cd4 helper t cells. the latter induce b cell maturation and antibody production. as a consequence, lymphocytes within the memory pool are poised to rapidly proliferate at the time of a subsequent infection. the "thymic vaccination" concept offers a novel way to alter the primary t cell repertoire through exposure of thymocytes t ... | 2004 | 15588284 |
| intestinal epithelial cells synthesize glucocorticoids and regulate t cell activation. | glucocorticoids (gcs) are important steroid hormones with widespread activities in metabolism, development, and immune regulation. the adrenal glands are the major source of gcs and release these hormones in response to psychological and immunological stress. however, there is increasing evidence that gcs may also be synthesized by nonadrenal tissues. here, we report that the intestinal mucosa expresses steroidogenic enzymes and releases the gc corticosterone in response to t cell activation. t ... | 2004 | 15596520 |
| role of tumor necrosis factor receptors in regulating cd8 t-cell responses during acute lymphocytic choriomeningitis virus infection. | the role of tumor necrosis factor (tnf) in regulating various phases of the antiviral t-cell response is incompletely understood. additionally, despite strong evidence ascribing a role for tnf in protecting against t-cell-dependent autoimmunity, the underlying mechanisms are still obscure. to address these issues, we have investigated the role of tumor necrosis factor receptors (tnfrs) i (p55r) and ii (p75r) in regulating cd8 t-cell responses to lymphocytic choriomeningitis virus (lcmv) with wil ... | 2005 | 15596816 |
| selective transduction of malignant glioma by lentiviral vectors pseudotyped with lymphocytic choriomeningitis virus glycoproteins. | malignant gliomas are the most frequent primary brain tumors and have a dismal prognosis due to their infiltrative growth. gene therapy using viral vectors represents an attractive alternative to conventional cancer therapies. in a previous study, we established lentiviral vectors pseudotyped with lymphocytic choriomeningitis virus (lcmv) glycoproteins (gps) and demonstrated transduction of human malignant glioma cells in culture. in the current approach, we compared the transduction efficacy of ... | 2004 | 15610609 |
| ontogeny and selection of the t cell repertoire in transgenic mice. | t cell receptor (tcr) transgenic mice have contributed to many aspects in understanding t cell ontogeny and selection of the peripheral repertoire. we have generated beta and alphabeta tcr transgenic mice, that predominantly express receptor chain(s) specific for the lymphocytic choriomeningitis virus glycoprotein, presented with the class i mhc h-2db. this beta chain uses vbeta8.1 and therefore reactivity with a self protein known as mls(a) may also be studied. the effects of a functional beta ... | 1989 | 15630811 |
| cutting edge: mhc class ii-restricted killing in vivo during viral infection. | class ii-restricted cd4 t cell-mediated killing of target cells has previously been documented in vitro but not in vivo. in this study, we demonstrate cd4-dependent mhc class ii-restricted killing in lymphocytic choriomeningitis virus-infected mice in vivo using an in vivo cytotoxicity assay that features class ii-expressing b cells as targets. | 2005 | 15634878 |
| t cells undergo rapid on/off but not on/off/on cycling of cytokine production in response to antigen. | inflammatory cytokines such as ifn-gamma and tnf produced by ag-stimulated cd4(+) and cd8(+) t cells are important in defense against microbial infection. however, production of these cytokines must be tightly regulated to prevent immunopathology. previous studies, conducted with balb/c mice, have suggested that 1) cd8(+) t cells maintain ifn-gamma production but transiently produce tnf in the continued presence of ag and 2) lymphocytic choriomeningitis virus-specific and in vitro-propagated eff ... | 2005 | 15634891 |
| arenavirus extinction through lethal mutagenesis. | viral hemorrhagic fevers represent serious human public health problems causing devastating and often lethal disease. several hemorrhagic fevers are caused by arenaviruses including lassa fever virus (lfv) and the south american viral hemorrhagic fevers (sahf). in recent years, increased air travel between africa and other areas has led to the importation of lfv into the us, europe, japan, and canada. this has raised awareness about arenaviruses as potential emerging viruses. moreover, because o ... | 2005 | 15649566 |
| toll-like receptor engagement converts t-cell autoreactivity into overt autoimmune disease. | autoimmune diabetes mellitus in humans is characterized by immunological destruction of pancreatic beta islet cells. we investigated the circumstances under which cd8(+) t cells specific for pancreatic beta-islet antigens induce disease in mice expressing lymphocytic choriomeningitis virus (lcmv) glycoprotein (gp) as a transgene under the control of the rat insulin promoter. in contrast to infection with lcmv, immunization with lcmv-gp derived peptide did not induce autoimmune diabetes despite l ... | 2005 | 15654326 |
| virus infection-associated bone marrow b cell depletion and impairment of humoral immunity to heterologous infection mediated by tnf-alpha/ltalpha. | we previously showed that influenza virus infection of mice induces a depletion of bone marrow b lineage cells due to apoptosis of early b cells mediated by a mechanism involving tnf-alpha/ltalpha. here we demonstrate that this effect is also observed with acute lymphocytic choriomeningitis virus (lcmv) infection and resulted in a deficiency of both splenic transitional b cells and mature follicular b cells. to determine whether there was an associated impairment of humoral immunity, we infected ... | 2005 | 15657949 |
| bone marrow is a preferred site for homeostatic proliferation of memory cd8 t cells. | proliferative renewal of memory cd8 t cells is essential for maintaining long-term immunity. in this study, we examined the contributions that various tissue microenvironments make toward the homeostatic proliferation of ag-specific memory cd8 t cells. we found that dividing memory t cells were present in both lymphoid and nonlymphoid tissues. however, the bone marrow was the preferred site for proliferation and contained a major pool of the most actively dividing memory cd8 t cells. adoptive tr ... | 2005 | 15661882 |
| transduction of human glial and neuronal tumor cells with different lentivirus vector pseudotypes. | lentiviral vectors have proven to be valuable tools for in vitro and in vivo gene delivery because they can transduce dividing and non-dividing cells efficiently, and mediate long-term gene expression. pseudotyping of lentiviral vectors with envelope proteins other than vsv-g has resulted in enhanced transduction of certain cell types and tissues. in order to improve lentiviral vector-based gene therapy for peripheral neuroectodermal and brain tumors, we compared the efficiency of eight differen ... | 2004 | 15662969 |
| ip-10 and type 1 diabetes: a question of time and location. | chemokines are key signal molecules that attract cells of the host immune system to the site of a potential threat. virus infections usually induce a massive chemokine and cytokine burst and therefore recruit a large plethora of leukocytes to the site of infection with the goal to restrict and abrogate viral spread. the down side of this massive excitation of the human defense system is non-specific activation of potentially self-reactive lymphocytes. coupled with an antigen-specific event, for ... | 2004 | 15672495 |
| the proline-rich homeodomain (prh/hex) protein is down-regulated in liver during infection with lymphocytic choriomeningitis virus. | the proline-rich homeodomain protein, prh/hex, participates in the early development of the brain, thyroid, and liver and in the later regenerative processes of damaged liver, vascular endothelial, and hematopoietic cells. a virulent strain of lymphocytic choriomeningitis virus (lcmv-we) that destroys hematopoietic, vascular, and liver functions also alters the transcription and subcellular localization of prh. a related virus (lcmv-arm) that does not cause disease in primates can infect cells w ... | 2005 | 15681447 |
| direct intralymphatic injection of peptide vaccines enhances immunogenicity. | research to enhance the efficiency of vaccines focuses mainly on improving either the adjuvant or the type and form of the antigen. this study evaluates the influence of the administration route on the efficiency of a peptide-based vaccine. peptide vaccines are generally administered subcutaneously or intradermally, from where they must reach secondary lymphatic organs to induce an immune response. we analyzed the efficacy of peptide vaccines administered directly into a lymph node. using a mhc ... | 2005 | 15682446 |
| rapid activation of spleen dendritic cell subsets following lymphocytic choriomeningitis virus infection of mice: analysis of the involvement of type 1 ifn. | in this study, we report the dynamic changes in activation and functions that occur in spleen dendritic cell (sdc) subsets following infection of mice with a natural murine pathogen, lymphocytic choriomeningitis virus (lcmv). within 24 h postinfection (pi), sdcs acquired the ability to stimulate naive lcmv-specific cd8+ t cells ex vivo. conventional (cd11chigh cd8+ and cd4+) sdc subsets rapidly up-regulated expression of costimulatory molecules and began to produce proinflammatory cytokines. the ... | 2005 | 15699111 |
| private specificities of cd8 t cell responses control patterns of heterologous immunity. | cd8 t cell cross-reactivity between viruses can play roles in protective heterologous immunity and damaging immunopathology. this cross-reactivity is sometimes predictable, such as between lymphocytic choriomeningitis virus (lcmv) and pichinde virus, where cross-reactive epitopes share six out of eight amino acids. here, however, we demonstrate more subtle and less predictable cross-reactivity between lcmv and the unrelated vaccinia virus (vv). epitope-specific t cell receptor usage differed bet ... | 2005 | 15710651 |
| viruses evade the immune system through type i interferon-mediated stat2-dependent, but stat1-independent, signaling. | understanding, treating, and preventing diseases caused by immunosuppression and/or persistent infections remain both a major challenge in biomedical research and an important health goal. for a virus or any infectious agent to persist, it must utilize strategies to suppress or evade the host's immune response. here, we report that two dissimilar viruses employ a common maneuver to cause a profound immunosuppression. measles virus (mv) and lymphocytic choriomeningitis virus (lcmv) interfere with ... | 2005 | 15723812 |
| long-term loss of canonical nkt cells following an acute virus infection. | nkt cell activation plays an important role in regulating innate and adaptive immunity during infection. we have previously found that there is a dramatic reduction in the nkt cell population on day 3 after an acute lymphocytic choriomeningitis virus (lcmv) infection. in this study, we report that this loss continued for at least 3 months and was not simply due to internalization of the tcr. concomitant with the decrease in nkt cells was an increase in the percentage of annexin v(+) nkt cells th ... | 2005 | 15724241 |
| myd88 is critical for the development of innate and adaptive immunity during acute lymphocytic choriomeningitis virus infection. | we investigated the roles of toll-like receptor 2 (tlr2) and myeloid differentiation factor 88 (myd88) in the course of a lymphocytic choriomeningitis virus (lcmv) infection and revealed the following: (i) studies of transfected cells and murine peritoneal macrophages demonstrated that tlr2 and myd88 are essential for the initial pro-inflammatory cytokine response (human il-8, mouse il-6) to lcmv; (ii) tlr2 knockout (ko) mice and myd88 ko mice challenged with lcmv produced less il-6 and monocyte ... | 2005 | 15724245 |
| inverse correlation between il-7 receptor expression and cd8 t cell exhaustion during persistent antigen stimulation. | persistence is a hallmark of infection by viruses such as hiv, hepatitis b virus, hepatitis c virus and lcmv. in the case of lcmv, persistence may often be associated with exhaustion of cd8(+) t cells. we demonstrate here that persistent antigen suppressed il-7ralpha expression and this correlated with t cell exhaustion and reduced expression of the anti-apoptotic molecule b cell leukemia/lymphoma 2 (bcl-2). in contrast, exposure to short-lived antigen only temporarily suppressed il-7ralpha expr ... | 2005 | 15724249 |
| cns activity of pokeweed anti-viral protein (pap) in mice infected with lymphocytic choriomeningitis virus (lcmv). | others and we have previously described the potent in vivo and in vitro activity of the broad-spectrum antiviral agent pap (pokeweed antiviral protein) against a wide range of viruses. the purpose of the present study was to further elucidate the anti-viral spectrum of pap by examining its effects on the survival of mice challenged with lymphocytic choriomeningitis virus (lcmv). | 2005 | 15725345 |
| the lymphocytic choriomeningitis virus envelope glycoprotein targets lentiviral gene transfer vector to neural progenitors in the murine brain. | feline immunodeficiency virus (fiv)-based lentiviral vectors can be targeted to restricted cell types by pseudotyping with envelopes from other viruses. an fiv vector expressing bacterial beta-galactosidase (beta-gal) and pseudotyped with lymphocytic choriomeningitis virus (lcmv) envelope glycoprotein was injected into postnatal mouse brain striatum to determine neural cell-type transduction. after 3 or 7.5 weeks, the beta-gal-expressing cells included astrocytes in the striatum and in the subve ... | 2005 | 15727934 |
| increased epitope-specific cd8+ t cells prevent murine coronavirus spread to the spinal cord and subsequent demyelination. | cd8+ t cells are important for clearance of neurotropic mouse hepatitis virus (mhv) strain a59, although their possible role in a59-induced demyelination is not well understood. we developed an adoptive-transfer model to more clearly elucidate the role of virus-specific cd8+ t cells during the acute and chronic phases of infection with a59 that is described as follows. c57bl/6 mice were infected with a recombinant a59 virus expressing the gp33 epitope, an h-2db-restricted cd8+ t-cell epitope enc ... | 2005 | 15731231 |
| complementarity in the supramolecular design of arenaviruses and retroviruses revealed by electron cryomicroscopy and image analysis. | arenaviruses are rodent-borne agents of diseases, including potentially lethal human hemorrhagic fevers. these enveloped viruses encapsidate a bisegmented ambisense single-stranded rna genome that can be packaged in variable copy number. electron cryomicroscopy and image analysis of new world pichinde and tacaribe arenaviruses and old world lymphocytic choriomeningitis virus revealed pleomorphic enveloped particles ranging in diameter from approximately 400 to approximately 2,000 a. the surface ... | 2005 | 15731275 |
| the cd4 molecule on cd8+ t lymphocytes directly enhances the immune response to viral and cellular antigens. | cd8+ t lymphocytes play a major role in cellular-mediated immune responses to foreign antigen. we have previously demonstrated that costimulation of purified human cd8+ t cells induces de novo expression of the cd4 molecule and that ligation of cd4 on this cell type modulates cd8+ t cell activity in vitro. herein, we investigate how the cd4 molecule expressed on murine cd8+ t cells contributes to cd8+ cell responses in vivo by employing adoptive transfer of cd8 cells from cd4 knockout mice into ... | 2005 | 15731353 |
| perforin and lymphohistiocytic proliferative disorders. | perforin is critical for cytotoxicity mediated by granules present in natural killer (nk) cells and cytotoxic t lymphocytes (ctls). perforin-deficient mice have impaired cytotoxicity by nk cells and ctls, resulting in failure to control infections with certain viruses or bacteria. infection of perforin-deficient mice with lymphocytic choriomeningitis virus results in haemophagocytic lymphohistiocytosis and elevated levels of pro-inflammatory cytokines. mutations throughout the perforin gene have ... | 2005 | 15755277 |
| complex memory t-cell phenotypes revealed by coexpression of cd62l and ccr7. | antigen-experienced t cells have been divided into cd62l+ ccr7+ central memory (tcm) and cd62l- ccr7- effector memory (tem) cells. here, we examined coexpression of cd62l and ccr7 in lymphocytic choriomeningitis virus-specific memory cd8 t cells from both lymphoid and nonlymphoid tissues. three main points emerged: firstly, memory cells frequently expressed a mixed cd62l- ccr7+ phenotype that differed from the phenotypes of classical tem and tcm cells; secondly, tcm cells were not restricted to ... | 2005 | 15767451 |
| dual role of the lymphocytic choriomeningitis virus intergenic region in transcription termination and virus propagation. | each genome segment of the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv), encodes two genes in ambisense orientation, separated by an intergenic region (igr). the 3' ends of subgenomic viral mrnas have been mapped to a stem-loop structure within the igr, suggesting structure-dependent transcription termination. we have studied the role of the lcmv igr by using a minigenome (mg) rescue system based on rna analogues of the short genome segment. an ambisense mg coding for chloramp ... | 2005 | 15767453 |
| suppression of viral infectivity through lethal defection. | rna viruses replicate with a very high error rate and give rise to heterogeneous, highly plastic populations able to adapt very rapidly to changing environments. viral diseases are thus difficult to control because of the appearance of drug-resistant mutants, and it becomes essential to seek mechanisms able to force the extinction of the quasispecies before adaptation emerges. an alternative to the use of conventional drugs consists in increasing the replication error rate through the use of mut ... | 2005 | 15767582 |
| defective b cell responses in the absence of sh2d1a. | more than half of patients with x-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein sh2d1a, suffer from an extreme susceptibility to epstein-barr virus. one-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. here we show that in sh2d1a(-/-) mice, both primary and secondary responses of all ig subclasses are severely impaired in response to specific antigens. because germinal centers were a ... | 2005 | 15774582 |
| priming of ctls by lymphocytic choriomeningitis virus depends on dendritic cells. | appropriate activation of naive cd8(+) t cells depends on the coordinated interaction of these cells with professional apc that present antigenic peptides in the context of mhc class i molecules. it is accepted that dendritic cells (dc) are efficient in activating naive t cells and are unique in their capacity to prime cd8(+) t cell responses against exogenous cell-associated ags. nevertheless, it is unclear whether epitopes, derived from endogenously synthesized proteins and presented by mhc cl ... | 2005 | 15778347 |
| immune modulation of the hypothalamic-pituitary-adrenal (hpa) axis during viral infection. | compelling data has been amassed indicating that soluble factors, or cytokines, emanating from the immune system can have profound effects on the neuroendocrine system, in particular the hypothalamic- pituitary-adrenal (hpa) axis. hpa activation by cytokines (via the release of glucocorticoids), in turn, has been found to play a critical role in restraining and shaping immune responses. thus, cytokine-hpa interactions represent a fundamental consideration regarding the maintenance of homeostasis ... | 2005 | 15802953 |
| interferon-gamma acts directly on cd8+ t cells to increase their abundance during virus infection. | interferon-gamma (ifngamma) is important in regulating the adaptive immune response, and most current evidence suggests that it exerts a negative (proapoptotic) effect on cd8(+) t cell responses. we have developed a novel technique of dual adoptive transfer, which allowed us to precisely compare, in normal mice, the in vivo antiviral responses of two t cell populations that differ only in their expression of the ifngamma receptor. we use this technique to show that, contrary to expectations, ifn ... | 2005 | 15809350 |