Publications

a single amino acid change in the glycoprotein of lymphocytic choriomeningitis virus is associated with the ability to cause growth hormone deficiency syndrome.	persistent infection of c3h/st mice with certain strains of lymphocytic choriomeningitis virus (lcmv) causes a growth hormone (gh) deficiency syndrome (ghds) manifested as growth retardation and hypoglycemia. infected mice show high levels of viral replication in the gh-producing cells in the anterior pituitary leading to decreased synthesis of gh mrna and protein despite the absence of detectable virus-induced cell structural damage. virus clones isolated from the ghds-negative lcmv we strain c ...	1996	8970965
variants able to cause growth hormone deficiency syndrome are present within the disease-nil we strain of lymphocytic choriomeningitis virus.	persistent infection of c3h/st mice with lymphocytic choriomeningitis virus (lcmv) strain armstrong leads to disordered growth and hypoglycemia. both host and viral determinants contribute to this growth hormone (gh) deficiency syndrome (ghds). development of the ghds correlates with the virus's ability to replicate in the gh-producing cells and cause reduced levels of gh synthesis. lcmv strain we infects few gh-producing cells and does not cause ghds in c3h/st mice. we show here that clonal var ...	1996	8971029
t-cell-mediated immunity to lymphocytic choriomeningitis virus in beta2-integrin (cd18)- and icam-1 (cd54)-deficient mice.	the t-cell response to lymphocytic choriomeningitis virus was studied in mice with deficient expression of beta2-integrins or icam-1. in such mice, the generation of virus-specific cytotoxic t lymphocytes was only slightly impaired and bystander activation was as extensive as that observed in wild-type mice. t-cell-mediated inflammation, assessed as primary footpad swelling and susceptibility to intracerebral infection, was slightly compromised only in beta2-integrin-deficient mice. however, ado ...	1996	8971031
viral infection of transgenic mice expressing a viral protein in oligodendrocytes leads to chronic central nervous system autoimmune disease.	one hypothesis for the etiology of central nervous system (cns) autoimmune disease is that infection by a virus sharing antigenic epitopes with cns antigens (molecular mimicry) elicits a virus-specific immune response that also recognizes self-epitopes. to address this hypothesis, transgenic mice were generated that express the nucleoprotein or glycoprotein of lymphocytic choriomeningitis virus (lcmv) as self in oligodendrocytes. intraperitoneal infection with lcmv strain armstrong led to infect ...	1996	8976191
homeostatic regulation of cd8+ t cells after antigen challenge in the absence of fas (cd95).	the role of fas in the homeostatic regulation of cd8+ t cells after antigen challenge was analyzed in the murine model of lymphocytic choriomeningitis virus (lcmv) infection. mice homozygous for the lpr mutation and carrying t cell receptor (tcr) alphabeta transgenes specific for the lcmv glycoprotein peptide aa 33-41 in the context of h-2db were used. five main results emerged: first, development of lymphadenopathy and of cd4- cd8- double-negative b220+ t cells in lpr mice was not inhibited by ...	1996	8977284
exacerbation of lymphocytic choriomeningitis in mice treated with the inducible nitric oxide synthase inhibitor aminoguanidine.	to elucidate the possible involvement of the inducible nitric oxide synthase (inos) and no in the development of lymphocytic choriomeningitis (lcm), the consequences of inhibition of inos by the inhibitor aminoguanidine was examined in mice following intracerebral infection with lcm virus (lcmv). aminoguanidine administration to mice infected with lcmv completely blocked increased plasma nitrate/nitrite levels and led to increased proinflammatory cytokine gene expression at early stages of lesio ...	1996	8982100
a comparison of efficacy and specificity of three nk depleting antibodies.	this study compares in vivo efficacy and specificity of the three nk cell depleting antibodies anti-asialo gm1, anti-nk 1.1 and the recently described tm beta 1, which is directed against the interleukin-2 receptor beta chain. all three antibodies are equally efficacious as assessed by abolishing nk mediated cytolytic activity induced by a high dose virus infection or poly ic against yac-1 targets. similarly, the generation of virus-specific cytotoxic t cells (ctl) was unimpaired after nk deplet ...	1996	8982356
long-term antibody production is sustained by antibody-secreting cells in the bone marrow following acute viral infection.	acute viral infection of humans induces virus-specific serum antibody production that often persists for decades. to better understand the nature of this long-term antiviral antibody response, we studied antiviral antibody production of mice acutely infected with lymphocytic choriomeningitis virus (lcmv). although this viral infection is resolved within 2 weeks, virus-specific serum antibody levels were maintained for > 300 days postinfection. the anatomic site of long-term antibody production w ...	1996	8993360
proteins expressed by dna vaccines induce both local and systemic immune responses.		1996	8993363
virus-induced autoimmune disease.	the breaking of tolerance or unresponsiveness to self-antigens, involving the activation of autoreactive lymphocytes, is a critical event leading to autoimmune diseases. the precise mechanisms by which this can occur are mostly unknown. viruses have been implicated in this process, among other etiological factors, such as genetic predisposition and cytokine activity. several ways have been proposed by which a viral infection might break tolerance to self and trigger an autoreactive cascade that ...	1996	8994870
transgenic mice to study viral pathogenesis and autoimmunity.		1996	9155662
intestinal intraepithelial lymphocytes respond to systemic lymphocytic choriomeningitis virus infection.	intestinal intraepithelial lymphocytes (iel) are a population of cells consisting mostly of cd8+ t lymphocytes. although their function is unknown, because of their location within the epithelium it has been postulated that iel may be involved in defense against infection of the gut mucosa by pathogens including viruses. to address this issue, we have examined iel populations from balb/c mice systemically infected with lymphocytic choriomeningitis virus (lcmv). viral infection induced a virus-sp ...	1996	8603424
virus-induced autoimmune disease: transgenic approach to mimic insulin-dependent diabetes mellitus and multiple sclerosis.		1996	8608726
persistent dentate granule cell hyperexcitability after neonatal infection with lymphocytic choriomeningitis virus.	infection of neonatal lewis rats with lymphocytic choriomeningitis virus (lcmv) produces distinct retinal, cerebellar, and hippocampal neuropathology. to understand the neurophysiological consequences of lcmv-induced hippocampal pathology, we studied evoked monosynaptic potentials and electro-encephalographic (eeg) activity in the dentate gyrus and ca1 and ca3 subfields of the hippocampus in vivo. lewis rats were inoculated intracerebrally with lcmv at postnatal day 4. in rats studied 84-107 d p ...	1996	8613788
transforming growth factor-beta fails to inhibit allograft rejection or virus-induced autoimmune diabetes in transgenic mice.	transgenic mice whose pancreata express transforming growth factor-beta (tgf-beta) directed by an insulin promoter (ins-tgf-beta mice) were used to assess the effect of local tgf-beta1 on allograft rejection and on autoimmune diabetes occurring as a cross-reaction to viral antigens. pancreatic tgf-beta1 did not delay allograft rejection, nor did it inhibit autoimmune diabetes after lymphocytic choriomeningitis infection of double transgenic mice (lcmv/tgf-beta1 mice). these results suggest that ...	1996	8623195
modulation by gamma interferon of antiviral cell-mediated immune responses in vivo.	mice were infected with lymphocytic choriomeningitis virus and injected once 24 h later with a monoclonal antibody directed against gamma interferon. in comparison with controls, the increase of numbers of cd8+ t cells and the generation of virus-specific cytotoxic t lymphocytes in spleens and virus clearance from organs were diminished, as was the ability of spleen cells to transmit adoptive immunity to infected recipients. the same treatment slightly but consistently lessened rather than augme ...	1996	8627670
competitive selection in vivo by a cell for one variant over another: implications for rna virus quasispecies in vivo.	infidelity of genome applications of rna viruses leads to the generation of viral quasispecies both in vitro and in vivo. however, the biological significance of such generated variants in vivo is largely unknown and controversial. to study this issue, we continued our evaluation of the tropism of a lymphocytic choriomeningitis virus (lcmv) variant termed clone 13 with its parental virus clonal pool arm 53b (wild-type parent) for neuronal cells in vivo. earlier in vivo and in vitro studies noted ...	1996	8627703
antiviral cytotoxic t-cell memory by vaccination with recombinant listeria monocytogenes.	listeria monocytogenes is a facultative intracellular bacterium that is able to escape phagocytic vesicles and replicate in the cytoplasm of infected cells. as with viral vectors, this intracytoplasmic life cycle provides a means for introducing foreign proteins into the major histocompatibility complex class i pathway of antigen presentation. using recombinant l. monocytogenes (rlm) strains expressing the full-length nucleoprotein (np) or a single cytotoxic t-lymphocyte (ctl) epitope from lymph ...	1996	8627765
congenital lymphocytic choriomeningitis virus infection.		1996	8634744
cd40l-deficient mice show deficits in antiviral immunity and have an impaired memory cd8+ ctl response.	the ligand for cd40 (cd40l) is expressed on the surface of activated cd4+ t cells and its role in t-b cell collaborations and thymus-dependent humoral immunity is well established. recently, by generating cd40l-knockout mice, we have confirmed its previously described role in humoral immunity and defined another important function of this molecule in the in vivo clonal expansion of antigen-specific cd4+ t cells. here, we investigated the potential in vivo role of cd40l in antiviral immunity by e ...	1996	8642323
development of insulitis without diabetes in transgenic mice lacking perforin-dependent cytotoxicity.	it is widely accepted that t cells play an important role in the destruction of beta cells leading to autoimmune type i diabetes, but the involved effector mechanisms have remained unclear. we addressed this issue by testing the role of perforin-dependent cytotoxicity in a disease model involving transgenic mice expressing glycoprotein of lymphocytic choriomeningitis virus (lcmv-gp) in the beta cells of the endocrine pancreas. in such mice, lcmv infection leads to a potent lcmv-gp-specific t cel ...	1996	8642324
cd8 t cell memory in b cell-deficient mice.	antigen presentation by b cells and persistence of antigen-antibody complexes on follicular dendritic cells (fdc) have been implicated in sustaining t cell memory. in this study we have examined the role of b cells and antibody in the generation and maintenance of cd8+ cytotoxic t lymphocyte (ctl) memory. to address this issue we compared ctl responses to lymphocytic choriomeningitis virus (lcmv) in normal (+/+) versus b cell-deficient mice. the ctl response to acute lcmv infection can be broken ...	1996	8642326
cd40-cd40 ligand interactions are critical in t-b cooperation but not for other anti-viral cd4+ t cell functions.	cd40-cd40 ligand (cd40l) interaction is required for the generation of antibody responses to t-dependent antigens as well as for the development of germinal centers and memory b cells. the role of the cd40-cd40l interaction in the induction of antigen-specific. th cells and in mediating th cell effector functions other than cognate help for b cells is less well understood. using cd40- and cd40l-deficient mice together with lymphocytic choriomeningitis virus and vesicular stomatitis virus as vira ...	1996	8642330
viral cross talk: intracellular inactivation of the hepatitis b virus during an unrelated viral infection of the liver.	hepatitis b virus (hbv) infection is thought to be controlled by virus-specific cytotoxic t lymphocytes (ctl). we have recently shown that hbv-specific ctl can abolish hbv replication noncytopathically in the liver of transgenic mice by secreting tumor necrosis factor alpha (tnf-alpha) and interferon gamma (ifn-gamma) after antigen recognition. we now demonstrate that hepatocellular hbv replication is also abolished noncytopathically during lymphocytic choriomeningitis virus (lcmv) infection, an ...	1996	8643448
in vivo induction of ctl responses by recombinant adenylate cyclase of bordetella pertussis carrying viral cd8+ t cell epitopes.	exogenous ags enter the endosomal pathway and are presented to cd4+ t cells in association with class ii molecules whereas endogenously synthesized ags, such as viral proteins, are presented to cd8+ t cells in association with mhc class i molecules. therefore, most ctl activation strategies use live vectors although an alternative possibility could be to deliver the epitope into the cytosol by targeting it to an invasive nonreplicative vector. the adenylate cyclase toxin of bordetella pertussis ...	1996	8648115
induction of bystander t cell proliferation by viruses and type i interferon in vivo.	t cell proliferation in vivo is presumed to reflect a t cell receptor (tcr)-mediated polyclonal response directed to various environmental antigens. however, the massive proliferation of t cells seen in viral infections is suggestive of a bystander reaction driven by cytokines instead of the tcr. in mice, t cell proliferation in viral infections preferentially affected the cd44hi subset of cd8+ cells and was mimicked by injection of polyinosinic-polycytidylic acid [poly(i:c)], an inducer of type ...	1996	8658169
viral persistence in neurons alters synaptic plasticity and cognitive functions without destruction of brain cells.	neurons have a restricted expression of mhc heavy chain molecules which prevents presentation of antigens of infecting viruses. as a result, such infected cells escape immune surveillance and allow the establishment of noncytolytic persistent infection. here we show that a chronic noncytolytic viral infection both in vitro and in vivo selectively perturbed the expression of gap-43, a protein that plays a central role in neuronal plasticity processes accompanying learning and memory. gap-43 expre ...	1996	8661403
binding of viral antigens to major histocompatibility complex class i h-2db molecules is controlled by dominant negative elements at peptide non-anchor residues. implications for peptide selection and presentation.	binding of viral antigens to major histocompatibility complex (mhc) class i molecules is a critical step in the activation process of cd8(+) cytotoxic t lymphocytes. in this study, we investigated the impact of structural factors at non-anchor residues in peptide-mhc interaction using the model of lymphocytic choriomeningitis virus (lcmv) infection of its natural host, the mouse. altering viral genes by making reassortants, recombinants, and using synthetic peptides, cd8(+) cytotoxic t lymphocyt ...	1996	8663374
visualization, characterization, and turnover of cd8+ memory t cells in virus-infected hosts.	the cellular basis of t cell memory is a controversial issue and progress has been hampered by the inability to induce and to trace long-term memory t cells specific for a defined antigen in vivo. by using the murine model of lymphocytic choriomeningitis virus (lcmv) infection and an adoptive transfer system with cd8+ t cells from transgenic mice expressing an lcmv-specific t cell receptor, a population of authentic memory t cells specific for lcmv was generated and analyzed in vivo. the transge ...	1996	8666895
lfa-1-deficient mice show normal ctl responses to virus but fail to reject immunogenic tumor.	the leukocyte integrin lfa-1 (cd11a/cd18) plays an important role in lymphocyte recirculation and homotypic interactions. leukocytes from mice lacking cd11a displayed defects in in vitro homotypic aggregation, in proliferation in mixed lymphocyte reactions, and in response to mitogen. mutant mice mounted normal cytotoxic t cell (ctl) responses against systemic lcmv and vsv infections and showed normal ex vivo ctl function. however, lfa-1-deficient mice did not reject immunogenic tumors grafted i ...	1996	8666900
multiple immune abnormalities in tumor necrosis factor and lymphotoxin-alpha double-deficient mice.	to investigate the roles of tumor necrosis factor (tnf) and lymphotoxin (lt)-alpha in the development and function of the immune system, the tnf and ltalpha genes were simultaneously inactivated in mice by homologous recombination. these mutant mice are highly susceptible to listeria monocytogenes infection and resistant to endotoxic shock induced by the combined administration of d-galactosamine (d-gain) and lipopolysaccharide (lps). their splenic microarchitecture is disorganized, characterize ...	1996	8671586
virus-induced polyclonal t cell activation is followed by apoptosis: partitioning of cd8+ t cells based on alpha 4 integrin expression.	systemic infection with lymphocytic choriomeningitis virus (lcmv) is accompanied by marked splenomegaly, primarily reflecting the accumulation of cd8(+) t cells with an activated phenotype (e.g. vla-4hi). analysis of dna content using 7-aminoactinomycin-d revealed that as many as 30% of cd8(+) t cells are cycling around day 6 post-infection and that virtually all cycling cells express a high level of vla-4. in accord with the relatively stable cd4+ cell number, only few cycling cd4+ cells were o ...	1996	8671658
reduction of otherwise remarkably stable virus-specific cytotoxic t lymphocyte memory by heterologous viral infections.	experimental analyses of the acute cytotoxic t lymphocyte (ctl) response to viruses have focused on studying these infections in immunologically naive hosts. in the natural environment, however, viral ctl responses occur in hosts that are already immune to other infectious agents. to address which factors contribute to the maintenance and waning of immunological memory, the following study examined the frequencies of virus-specific ctl precursor cells (pctl) not only using the usual experimental ...	1996	8676069
prevalence of antibodies to arenaviruses in rodents from the southern and western united states: evidence for an arenavirus associated with the genus neotoma.	the objectives of this study were to extend our knowledge of the geographic distribution and rodent host range of arenaviruses in north america. sera from wild rodents collected from the southern and western united states were tested for antibody against tamiami, pichinde, junin, and lymphocytic choriomeningitis viruses, using an indirect fluorescent antibody test. antibody to at least one arenavirus was found in 220 (3.1%) of 7,106 rodents tested. the antibody-positive animals included mus musc ...	1996	8686773
seroepidemiological survey of lymphocytic choriomeningitis virus in wild house mice in china with particular reference to their subspecies.	serum samples from 337 wild house mice (mus musculus) from 35 sites in china, collected in 1992 and 1993, were examined for antibodies against lymphocytic choriomeningitis virus (lcmv). ten samples from eight sites were found to contain such antibodies. six of the eight positive sites were located in the territory of m. m. gansuensis. one of the other two sites was located in the territory of m. m. castaneus in southern china and the other site was in a habitat of m. m. castaneus which had invad ...	1996	8709868
molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in vivo.	studies with perforin-deficient mice have demonstrated that two independent mechanisms account for t cell-mediated cytotoxicity: a main pathway is mediated by the secretion of the pore-forming protein perforin by the cytotoxic t cell, whereas an alternative nonsecretory pathway relies on the interaction of the fas ligand that is upregulated during t cell activation with the apoptosis-inducing fas molecule on the target cell. nk cells use the former pathway exclusively. the protective role of the ...	1996	8717513
specific cytotoxic t cells eliminate b cells producing virus-neutralizing antibodies [corrected].	in medically important infections with cytopathic viruses, neutralizing antibodies are generated within 6-14 days. in contrast, such protective antibodies appear late (50-150 days) after infection with immunodeficiency virus (hiv) and hepatitis b virus (hbv) in humans, or lymphocytic choriomeningitis virus (lcmv) in mice. however, during these infections, non-neutralizing antibodies appear much earlier. it has been proposed that t cells suppress antibody responses generally and against viruses i ...	1996	8751445
duration of tcr stimulation determines costimulatory requirement of t cells.	current models suggest that t cells that receive only signal-1 through antigenic stimulation of the t cell receptor (tcr) become anergic, but will mount an immune response when a costimulatory signal-2 is provided. using mice deficient for an important costimulatory molecule, cd28, we show that a transient signal-1 alone, either through infection with an abortively replicating virus, or through injection of viral peptide, anergizes cd8+ t cells, demonstrating the biological relevance of t cell a ...	1996	8758893
on the role of antigen in maintaining cytotoxic t-cell memory.	this study evaluated whether t-cell memory reflects increased precursor frequencies of specific long-lived t cells and/or a low-level immune response against some form of persistent antigen. antivirally protective cd8+ t-cell memory was analyzed mostly in the original vaccinated host to assess the role of antigen in its maintenance. t-cell mediated resistance against reinfection was measured in the spleen and in peripheral solid organs with protocols that excluded protection by antibodies. in vi ...	1996	8790397
different roles for cytotoxic t cells in the control of infections with cytopathic versus noncytopathic viruses.	the assessment of the role of t-cell-mediated cytotoxicity in immunity to viral infections has been difficult to address directly and therefore has been controversial. recent experiments with perforin-deficient mice have shown that cytotoxicity is crucial for the resolution of infection with lymphocytic choriomeningitis virus but not for the resolution of infection with vaccinia, vesicular stomatitis, semliki forest or influenza virus. these findings may reflect the general pattern that t-cell-m ...	1996	8794015
murine infection with lymphocytic choriomeningitis virus following gastric inoculation.	laboratory studies of arenaviruses have been limited to parenteral routes of infection; however, recent epidemiological studies implicate virus ingestion as a natural route of infection. accordingly, we developed a model for oral and gastric infection with lymphocytic choriomeningitis virus to enable studies of mucosal transmission and vaccination by this additional route.	1996	8794369
selective activation of cd8 t cell effector functions by epitope variants of lymphocytic choriomeningitis virus glycoprotein.	we provide evidence for selective activation of different effector functions of cd8+ t lymphocytes by altered peptide ligands. a t cell epitope from the glycoprotein of lymphocytic choriomeningitis virus (p33-41) and single amino acid variants thereof were used for primary in vitro induction of ctl clones. when the ctl were analyzed for cytotoxicity, proliferation, ifn-gamma production, and ca2+ mobilization, we found that some of the clones showed activation of only their cytotoxic effector fun ...	1996	8805633
suppression of lymphocytic choriomeningitis virus--induced growth hormone deficiency syndrome by disease-negative virus variants.	populations of rna viruses consist of heterogeneous mixtures of related genomes (quasispecies). isolation of variants present at low levels within a population can result in clonal virus populations which display markedly different phenotypes upon infection of the host. the mechanisms by which these variants are maintained within the original quasispecies are not understood. certain strains of lymphocytic choriomeningitis virus (lcmv) cause a growth hormone deficiency syndrome (ghds) when inocul ...	1996	8806545
function and regulation of natural killer (nk) cells during viral infections: characterization of responses in vivo	although in vitro systems have provided important information about the composition and nature of various immune responses, understanding physiologically relevant function and regulation requires evaluating in vivo conditions. two different models of acute viral infections have made possible the characterization of a variety of responses to these agents, including natural killer (nk) cell activation and regulation during infection; these are mouse infections with lymphocytic choriomeningitis vir ...	1996	8812691
t cell responses are governed by avidity and co-stimulatory thresholds.	we analyzed the avidity and cd28-mediated co-stimulatory requirements for the activation of t cells in vivo and in vitro. the strength of the t cell/antigen-presenting cell interaction was varied by using altered peptide ligands for stimulation. co-stimulatory requirements were studied using t cells from cd28-deficient mice. the results indicate that t cell activation is not an all-or-nothing event, but occurs in distinct steps. for each step, a certain avidity, co-stimulatory threshold or both, ...	1996	8814240
immunity to viruses in b cell-deficient mice: influence of antibodies on virus persistence and on t cell memory.	mice rendered b cell deficient by targeted disruption of the immunoglobulin mu chain gene (igm-/- mice) were used to analyze the role of antibodies and b cells in viral infections; homozygous igm-/- mice were bred in a way to avoid transmission of maternal antibodies. after infection with vesicular stomatitis virus (vsv), igm-/- mice developed paralytic disease and subsequently died, whereas c57bl/6 control mice or igm-/- mice passively protected with vsv-neutralizing antibodies survived. furthe ...	1996	8814275
nk cell trafficking and cytokine expression in splenic compartments after ifn induction and viral infection.	studies were undertaken to characterize mechanisms for nk cell cytokine delivery in vivo. conditions of systemic ifn-beta expression elicited by polyinosinic-polycytidylic acid (poly(i:c)) treatment or ifn-alpha beta production during lymphocytic choriomeningitis virus or murine cytomegalovirus infections resulted in profound splenic histologic changes, with relocalization of nucleated cells from red to white pulp regions. cell-trafficking experiments, with fluorescently labeled populations, sho ...	1996	8816415
exhaustion of ctl memory and recrudescence of viremia in lymphocytic choriomeningitis virus-infected mhc class ii-deficient mice and b cell-deficient mice.	to study the contribution of cd4+ t cells and b cells to antiviral immunity and long term virus control, mhc class ii-deficient and b cell-deficient mice were infected with lymphocytic choriomeningitis virus. in class ii-deficient mice, which lack cd4+ t cells, the primary ctl response is virtually intact, and the infection is initially controlled in most organ sites including the blood. however, approximately 2 mo postinfection, ctl memory cannot be detected, and recrudescence of viremia to tit ...	1996	8816417
oral insulin treatment suppresses virus-induced antigen-specific destruction of beta cells and prevents autoimmune diabetes in transgenic mice.	oral administration of self-antigens has been proposed as a therapy to prevent and treat autoimmune diseases. here we report that oral treatment with insulin prevents virus-induced insulin-dependent diabetes mellitus (iddm) in a transgenic (tg) mouse model. such mice express the viral nucleoprotein (np) of lymphocytic choriomeningitis virus (lcmv) under control of the rat insulin promoter in their pancreatic beta cells and < 2% spontaneously develop diabetes. however, 2 mo after challenge with l ...	1996	8823297
lymphocytic choriomeningitis virus: a neglected central nervous system pathogen.		1996	8825010
antiviral immune responses of mice lacking mhc class ii or its associated invariant chain.	induction of t-helper cells and t-b cell interaction have been considered to critically depend upon recognition of major histocompatibility complex (mhc) class ii molecules by the t cell receptor. mice lacking either mhc class ii molecules (class ii(0/0) mice) or its associated invariant chain (ii0/0 mice) provide new opportunities to test this premise. immune responses to some protein antigens have been studied in these mice; little is known about their ability to withstand viral infections. we ...	1996	8548834
the cd45rb-associated epitope defined by monoclonal antibody cz-1 is an activation and memory marker for mouse cd4 t cells.	monoclonal antibody cz-1 defines a novel sialic acid-dependent cd45rb-associated epitope. the cz-1 antigen is expressed on the subpopulation of cd4 t cells that proliferate in response to il-2. because il-2 responsiveness often denotes t cell activation, we examined the expression of the cz-1 antigen on cd4 t cells taken from mice at various times during an infection with lymphocytic choriomeningitis virus (lcmv). the blast-sized cd4 t cells at day 6 postinfection were cz-1+. further cell surfac ...	1996	8548845
cd4-deficient mice have reduced levels of memory cytotoxic t lymphocytes after immunization and show diminished resistance to subsequent virus challenge.	although primary antiviral cd8+ cytotoxic t lymphocytes (ctl) can be induced in mice depleted of cd4+ t cells, the role of cd4+ t lymphocytes in the generation and maintenance of antiviral memory ctl is uncertain. this question, and the consequences upon vaccine-mediated protection, were investigated in transgenic cd4 knockout (cd4ko) mice, which lack cd4+ t lymphocytes. infection of immunocompetent c57bl/6 mice with lymphocytic choriomeningitis virus (lcmv), or with recombinant vaccinia viruses ...	1996	8551565
an absolute and restricted requirement for il-12 in natural killer cell ifn-gamma production and antiviral defense. studies of natural killer and t cell responses in contrasting viral infections.	il-12 is a potent induce of ifn-gamma and is associated with a wide variety of immunoregulatory activities. using murine cmv (mcmv) and lymphocytic choriomeningitis virus (lcmv) models of acute viral infection, we show here that il-12 is integrally involved in certain aspects of antiviral immunity. experiments evaluating the production and function of il-12 demonstrated the induction of biologically active factor early during smith strain mcmv, but not armstrong strain lcmv, infection. the mcmv- ...	1996	8557990
multifocal defects in immune responses in relb-deficient mice.	mice with a targeted disruption of the rel/nuclear factor-kappab family member relb develop a complex inflammatory phenotype, myeloid hyperplasia, and splenomegaly due to extramedullary hemopoiesis. in this work, we report that relb-deficient mice, in addition to the pathologic changes, were highly susceptible to infection by the facultative intracellular bacterium listeria monocytogenes. relb binds transcriptionally active kappab motifs in the tnf-alpha promoter in normal cells, and in vitro st ...	1997	9164938
cytolytically active memory ctl present in lymphocytic choriomeningitis virus-immune mice after clearance of virus infection.	generally, it has been assumed that memory t cells are dormant and inactive cells in the absence of their specific ag. recent work has challenged this assumption by showing that a portion of the cd8+ memory t cell pool is in cycle. in this study, we demonstrate that a significant number of blast-size memory cd8+ t cells in mice, long after lymphocytic choriomeningitis virus (lcmv) infection, mediate cytolysis against highly sensitive targets without any in vivo or in vitro restimulation and expa ...	1997	9164957
differential immune recognition of lcmv nucleoprotein and glycoprotein in transgenic mice expressing lcmv cdna genes.	we have generated doubly transgenic (dt) mice that independently express cdna genes for the nucleocapsid protein (np) and the surface glycoproteins (gp) of lymphocytic choriomeningitis virus (lcmv). by rt-pcr, transcription of both transgenes was detected at low levels in brain and kidney but was not observed in the thymus. additionally, transcription of the gp transgene was observed in the spleen. following challenge with exogenous lcmv, an anti-np ctl response was induced in lcmv-infected dt m ...	1997	9168891
peptide antigen treatment of naive and virus-immune mice: antigen-specific tolerance versus immunopathology.	peptide-specific down-regulation of t cell responses may represent a powerful tool to intervene in autoimmune diseases or graft rejections. it is therefore important to know whether peptide treatment tolerizes both naive and antigen-experienced memory t lymphocytes. here we show that a major histocompatibility complex class i binding peptide, derived from the glycoprotein (gp33 peptide) of lymphocytic choriomeningitis virus (lcmv), specifically tolerized naive cytotoxic t lymphocytes (ctl) when ...	1997	9175830
on the key role of secondary lymphoid organs in antiviral immune responses studied in alymphoplastic (aly/aly) and spleenless (hox11(-)/-) mutant mice.	the role of the spleen and of other organized secondary lymphoid organs for the induction of protective antiviral immune responses was evaluated in orphan homeobox gene 11 knockout mice (hox11(-/-)) lacking the spleen, and in homozygous alymphoplastic mutant mice (aly/aly) possessing a structurally altered spleen but lacking lymph nodes and peyer's patches. absence of the spleen had no major effects on the immune response, other than delaying the antibody response by 1-2 d. in aly/aly mice, the ...	1997	9182687
uncovering subdominant cytotoxic t-lymphocyte responses in lymphocytic choriomeningitis virus-infected balb/c mice.	the cytotoxic t-lymphocyte response against lymphocytic choriomeningitis virus (lcmv) in balb/c mice is predominantly directed against a single, ld-restricted epitope in the viral nucleoprotein (residues 118 to 126). to investigate whether any kd/dd-restricted responses were activated but did not expand during the primary response, we used a balb/c mutant, balb/c-h-2dm2, which does not express the ld molecule. splenocytes from lcmv-infected balb/c mice were transferred into irradiated balb/c-h-2 ...	1997	9188577
functional in vivo mhc class ii loading by endogenously synthesized glycoprotein during viral infection.	mhc class ii presentation of antigenic peptides derived from soluble proteins is usually preceded by antigenic uptake via (nonreceptor-mediated) endocytosis by professional apcs, followed by processing in endosomal compartments. although in vitro alternative pathways for mhc class ii loading have been described for certain intracellularly synthesized proteins, the importance of these pathways has not been assessed in vivo. we have shown previously that endogenously produced membrane-associated g ...	1997	9190921
pathogenesis and treatment of virus-induced autoimmune diabetes: novel insights gained from the rip-lcmv transgenic mouse model.		1997	9191170
a critical role for neutralizing-antibody-producing b cells, cd4(+) t cells, and interferons in persistent and acute infections of mice with lymphocytic choriomeningitis virus: implications for adoptive immunotherapy of virus carriers.	this study demonstrates that neutralizing-antibody-producing b cells, cd4(+) t cells, and interferons (ifns) are of key importance in virus control both in adoptive immunotherapy of persistent infection and in the late phase of acute infection with the we strain of lymphocytic choriomeningitis virus (lcmv). we report the following results. (i) clearance of lcmv-we from c57bl/6 carrier mice by adoptive transfer of memory spleen cells requires b cells and cd4(+) t cells but not necessarily cd8(+) ...	1997	9192659
congenital lymphocytic choriomeningitis virus syndrome: a disease that mimics congenital toxoplasmosis or cytomegalovirus infection.	to describe the clinical characteristics of intrauterine infection with lymphocytic choriomeningitis (lcm) virus, an uncommonly recognized cause of congenital viral infection.	1997	9200383
recombinant parvovirus-like particles as an antigen carrier: a novel nonreplicative exogenous antigen to elicit protective antiviral cytotoxic t cells.	to develop a strategy that promotes efficient antiviral immunity, hybrid virus-like particles (vlp) were prepared by self-assembly of the modified porcine parvovirus vp2 capsid protein carrying a cd8(+) t cell epitope from the lymphocytic choriomeningitis virus nucleoprotein. immunization of mice with these hybrid pseudoparticles, without adjuvant, induced strong cytotoxic t lymphocyte (ctl) responses against both peptide-coated- or virus-infected-target cells. this cd8(+) class i-restricted cyt ...	1997	9207121
sensitization to lipopolysaccharide in mice with asymptomatic viral infection: role of t cell-dependent production of interferon-gamma.	the interplay between viral infection and lipopolysaccharide (lps) was studied. infection with a noncytopathogenic virus, lymphocytic choriomeningitis virus (lcmv), was found to sensitize mice to low doses of lps. in vivo, this hypersensitivity correlated with hyperproduction of tumor necrosis factor-alpha (tnf-alpha), and in vitro, lps-stimulated splenic adherent cells produced increased amounts of tnf-alpha. hyperproduction of tnf-alpha was temporally correlated with virus-induced production o ...	1997	9207361
pathological changes in the islet milieu precede infiltration of islets and destruction of beta-cells by autoreactive lymphocytes in a transgenic model of virus-induced iddm.	rip-lcmv transgenic mice that express the viral glycoprotein (gp) or nucleoprotein (np) from lymphocytic choriomeningitis virus (lcmv) under control of the rat insulin promoter (rip) in pancreatic beta-cells develop autoimmune diabetes (iddm) after infection with lcmv. previous reports have described that the viral infection activates naive, potentially autoreactive cd8+ cytotoxic t-lymphocytes (ctl) that are present in the periphery of these mice, thus leading to the breaking of immunological u ...	1997	9218748
[the dynamics of the formation of igg subclasses in balb/c and cba mice infected with the lcm, lassa and mopeia viruses and their role in diagnosis].	the dynamics of the induction of individual igg subclasses in balb/c and cba mice and their role on the diagnostics of arenaviruses lcm, lassa and mopeia was studied. the study demonstrated that in solid-phase enzyme immunoassay (eia) isotypes igg2a and igg2b to virus mopeia could be used for the differentiation of virus mopeia from viruses lcm and lassa, and the antigen of virus mopeia could be used for the preparation of diagnostic eia systems not only to nonpathogenic virus mopeia, but also t ...	1997	9221657
functional management of an antiviral cytotoxic t-cell response.	lymphocytic choriomeningitis virus (lcmv) is known to induce strong, polyclonal cytotoxic t-lymphocyte (ctl) responses. using a set of variant peptides derived from the major ctl epitope of lcmv, we analyzed the functional fine specificity of the lcmv-specific ctl response. during the primary response, almost all the tested peptides were recognized. in contrast, the secondary response was purged of all minor cross-reactivities and very few peptides were significantly recognized. this study is th ...	1997	9223463
infection of c3heb/fej mice with the docile strain of lymphocytic choriomeningitis virus induces autoantibodies specific for erythrocyte band 3.	c3heb/fej mice infected with the docile strain of lymphocytic choriomeningitis virus (lcmv-d) develop a persistent infection with a transient haemolytic anaemia. immunoglobulin can be eluted from the red blood cells (rbc) of these mice but it cannot be detected on the rbc by a conventional antiglobulin test. the present study demonstrates that rbc from such mice bear erythrocyte autoantibodies which are predominantly of the igg2a subclass, with lower levels of autoantibodies of the igg1, igg2b a ...	1997	9227323
a serological indication of the existence of a guineapig poliovirus.	attempts were made to clarify whether laboratory guineapigs may harbour a poliovirus which, in 1911, was described as the cause of a disease called guineapig lameness. by the use of elisa for antibodies against the poliovirus, theiler's murine encephalomyelitis virus (tmev), it was shown that two pet shop guineapigs suffering from lameness had extremely high titres against poliovirus, while healthy guineapigs from the same pet shop were negative. clearly positive results were also found in 35 ou ...	1997	9230501
the signal sequence of lymphocytic choriomeningitis virus contains an immunodominant cytotoxic t cell epitope that is restricted by both h-2d(b) and h-2k(b) molecules.	infection of h-2b mice with lymphocytic choriomeningitis virus (lcmv) generates three well-characterized h-2d(b)-restricted immunodominant epitopes delineated in the np, gp1, and gp2 proteins. here we report that the h-2d(b)-restricted gp1 epitope gp33-41/43 (kavynfatc/gi) located in the signal sequence of lcmv is also the immunodominant epitope recognized by ctl at the surface of the same infected cells in the context of h-2k(b) restriction. the gp1 epitope bound to h-2d(b) and h-2k(b) molecule ...	1997	9234947
age distribution of lymphocytic choriomeningitis virus serum antibody in birmingham, alabama: evidence of a decreased risk of infection.	lymphocytic choriomeningitis virus (lcmv) is an arenavirus that causes human disease ranging from a mild, flu-like illness to meningitis. infections occur principally in and around the home due to contact with infected mice. data on the incidence of lcmv infection in the united states are scarce but suggest that the risk of infection may have decreased over the past 30-40 years. to examine this hypothesis, sera from an age-stratified sample of hospital patients in birmingham, alabama were tested ...	1997	9242315
timed appearance of lymphocytic choriomeningitis virus after gastric inoculation of mice.	arenaviruses present an emerging health threat in agrarian areas of africa and south america; however, the natural routes of arenaviral infections are not clearly understood. our previous studies with lymphocytic choriomeningitis virus (lcmv), the prototype arenavirus, implicate oral and intragastric routes as natural routes of infection. our studies raised many questions about the primary site of infection and the route of dissemination after gastric infection. in this report, we use in situ hy ...	1997	9250174
similar ligand densities required for restimulation and effector function of cytotoxic t cells.	this study compared ligand densities on antigen-presenting cells (apcs) needed for in vitro restimulation of in vivo primed t cells and for in vitro assessed t cell effector function. spleen cells of lymphocytic choriomeningitis virus (lcmv)-primed mice were restimulated in vitro with graded amounts of virus-derived peptides using macrophages or a cloned dendritic cell line as apcs. to test for effector function of these cytotoxic t cells, the same apcs pulsed with graded amounts of the peptides ...	1997	9259767
a novel type of defective viral genome suggests a unique strategy to establish and maintain persistent lymphocytic choriomeningitis virus infections.	defective interfering rnas have long been thought to be a causal factor of persistent rna virus infections. here we describe a novel type of defective genome of lymphocytic choriomeningitis virus and the unique mechanism by which these rnas appear to contribute to the establishment and maintenance of persistent infection. the defective genomes have short deletions in the untranslated regions at their termini and additional nontemplated terminal nucleotides. this and previous work from our labora ...	1997	9261400
immunological control of murine gammaherpesvirus infection is independent of perforin.	perforin-mediated cytotoxic t cell killing has been suggested to be of importance in the control of noncytopathic virus infections, based on studies with lymphocytic choriomeningitis virus (lcmv). we examined the role of perforin in a mouse model of gammaherpesvirus infection using transgenic perforin-deficient mice. previous work from this laboratory has shown that cd8 t cells are essential for the resolution of the acute lung infection and control of latently infected b cells in murine gamma-h ...	1997	9267003
protection of mice by an attenuated variant against the wild-type lymphocytic choriomeningitis virus.	l cells persistently infected with strain armstrong lymphocytic choriomeningitis virus generated a variant which failed to develop the lethal neurologic disease after application to the brain. this virus was able to protect mice from the fatal consequences when inoculated intracerebrally prior to challenge with wild-type (wt) virus. after infection of mice with the attenuated variant and thereafter with the wt virus, production of the latter was extraordinarily reduced. as expected, virus elimin ...	1997	9268768
self antigens expressed by solid tumors do not efficiently stimulate naive or activated t cells: implications for immunotherapy.	induction and maintenance of cytotoxic t lymphocyte (ctl) activity specific for a primary endogenous tumor was investigated in vivo. the simian virus 40 t antigen (tag) expressed under the control of the rat insulin promoter (rip) induced pancreatic beta-cell tumors producing insulin, causing progressive hypoglycemia. as an endogenous tumor antigen, the lymphocytic choriomeningitis virus (lcmv) glycoprotein (gp) was introduced also under the control of the rip. no significant spontaneous ctl act ...	1997	9271580
expression of adenoviral e3 transgenes in beta cells prevents autoimmune diabetes.	the adenovirus (ad) genome contains immunoregulatory and cytokine inhibitory genes that are presumed to function in facilitating acute infection or in establishing persistence in vivo. some of these genes are clustered in early region 3 (e3), which contains a 19-kda glycoprotein (gp19) that inhibits the transport of selected class i major histocompatibility complex (mhc) molecules out of the endoplasmic reticulum. in addition, the e3 region contains three protein inhibitors of the cytolytic func ...	1997	9275207
specific recognition of thymic self-peptides induces the positive selection of cytotoxic t lymphocytes.	to understand how thymic selection gives rise to t cells that are capable of major histocompatibility complex (mhc)-restricted recognition of antigen but are tolerant of self, we directly examined how peptide/mhc ligands expressed on thymic epithelial cells trigger the positive selection of immature thymocytes. we demonstrate that abundant self-peptides, purified from the h-2d(b) molecules of thymic epithelial cells, are specifically recognized during the positive selection of cd8+ t cells, impl ...	1997	9285407
deficits in discriminated learning remain despite clearance of long-term persistent viral infection in mice.	mice persistently infected with lymphocytic choriomeningitis virus (lcmv) exhibit impaired learning ability. in this report, we determined whether clearance of the virus was associated with restoration of behavioral function. neonatal balb/cbyj mice were persistently infected with lcmv and tested as adults in a nonconditional spatial discrimination task. the presence of viral proteins in neurons was confirmed immunohistochemically and infectious virus was quantified in the blood by plaque assay. ...	1997	9291234
bone marrow contains virus-specific cytotoxic t lymphocytes.	immunizing bone marrow donors prior to bone marrow transplant (bmt) has the potential for adoptively transferring specific immunity against opportunistic pathogens. studies have shown that long-term antibody production occurs in the bone marrow and that specific humoral immunity may be transferred from donor to recipient following bmt. however, the magnitude and duration of t-cell memory in the bone marrow compartment has not been adequately investigated. in this study, virus-specific cd8+ t-cel ...	1997	9292550
normal thymic selection, normal viability and decreased lymphoproliferation in t cell receptor-transgenic ctla-4-deficient mice.	ctla-4 is a t cell surface receptor essential for the negative regulation of t cell activation. in the ctla-4-deficient mouse, a dramatic accumulation of activated peripheral t cells effects extensive damage to host tissues, resulting in mortality within 5 weeks of age. to determine whether the accumulation of activated t cells in ctla-4(-/-) mice is due to a defect in thymic selection, we examined negative selection in ctla-4(-/-) mice using two transgenic t cell receptor (tcr) models of thymic ...	1997	9295023
tumor-peptide-pulsed dendritic cells isolated from spleen or cultured in vitro from bone marrow precursors can provide protection against tumor challenge.	dendritic cells (dc) purified from murine spleen or generated in vitro from bone marrow precursors were compared for their respective abilities to stimulate t cell responses and provide tumor protection in vivo. in vitro incubation with synthetic tumor peptide conferred on both dc populations the ability to induce proliferation of tumor-peptide-specific t cells in vitro. spleen dc were reproducibly about twofold more effective than bone-marrow-derived dc in this assay. both dc populations could ...	1997	9298937
antiviral immune responses in itk-deficient mice.	mice lacking itk, a t-cell-specific protein tyrosine kinase, have reduced numbers of t cells and reduced responses to allogeneic major histocompatibility molecules. this study analyzed antiviral immune responses in mice deficient for itk. primary cytotoxic t-lymphocyte (ctl) responses were analyzed after infection with lymphocytic choriomeningitis virus (lcmv), vaccinia virus (vv), and vesicular stomatitis virus (vsv). ex vivo ctl activity was consistently reduced by a factor of two to six for t ...	1997	9311799
chemokine gene expression in the brains of mice with lymphocytic choriomeningitis.	chemokines are pivotal in the trafficking of leukocytes. in the present study, we examined the expression of multiple chemokine genes during the course of lymphocytic choriomeningitis (lcm) in mice. in noninfected mice, no detectable chemokine gene expression was found in the brain; however, by day 3 postinfection, the induction of a number of chemokine mrnas was observed as follows (in order from the greatest to the least): cytokine responsive gene-2 or interferon-inducible 10-kda protein (crg- ...	1997	9311871
neonatal dna immunization with a plasmid encoding an internal viral protein is effective in the presence of maternal antibodies and protects against subsequent viral challenge.	conventional vaccines are remarkably effective in adults but are much less successful in the very young, who are less able to initiate a mature immune response and who may carry maternal antibodies which inactivate standard vaccines. we set out to determine whether dna immunization might circumvent these problems. we have previously shown that intramuscular injection of plasmid dna encoding the nucleoprotein (np) gene of lymphocytic choriomeningitis virus (lcmv) is capable of inducing immune res ...	1997	9311877
recombinant listeria monocytogenes as a live vaccine vehicle and a probe for studying cell-mediated immunity.	the ability of listeria monocytogenes (l. monocytogenes) to enter the cytosol of host cells allows secreted proteins to efficiently enter the endogenous antigen-processing pathway leading to presentation by mhc class i molecules. l. monocytogenes has recently been exploited as a live vaccine vehicle for the induction of immunological memory against heterologous antigens. we have established a genetic system for site-specific integration of antigen expression cassettes into the listeria genome wh ...	1997	9314083
early but not late burn wound excision partially restores viral-specific t lymphocyte cytotoxicity.	early burn wound excision restores immunocompetence and improves patient survival, but the exact mechanisms have not yet been defined. burn injury impairs cytotoxic t lymphocyte (ctl) activity as a function of burn size, increasing the risk of infection. the purpose of this study was to determine if early wound excision improved viral-specific ctl function.	1997	9314305
peptide-induced t cell receptor down-regulation on naive t cells predicts agonist/partial agonist properties and strictly correlates with t cell activation.	recent experiments defining t cell agonists, partial agonists and antagonists have suggested that the t cell can discriminate between subtle differences in interactions leading to t cell activation. to further understand the complexities of t cell activation, we have analyzed the requirements for the induction of a variety of effector functions using naive t cells and a variety of altered peptide ligands. using a strong agonist peptide, massive t cell receptor (tcr) down-regulation correlated wi ...	1997	9341759
virus-specific, cd8+ major histocompatibility complex class i-restricted cytotoxic t lymphocytes in lymphocytic choriomeningitis virus-infected beta2-microglobulin-deficient mice.	following infection with lymphocytic choriomeningitis virus (lcmv), normal adult mice generate virus-specific, major histocompatibility complex (mhc) class i-restricted cytotoxic t lymphocytes (ctl) which clear the virus after intraperitoneal infection or cause death following intracranial (i.c.) infection. we have investigated the response of beta2-microglobulin-deficient (beta2m-) mice of the h-2d haplotype (kod mice) to lcmv infection. unlike h-2b beta2m- mice, which generate cd4+ mhc class i ...	1997	9343195
dna immunization: ubiquitination of a viral protein enhances cytotoxic t-lymphocyte induction and antiviral protection but abrogates antibody induction.	dna immunization can induce cytotoxic t lymphocytes (ctl), antibodies, and protection against microbial challenge. the underlying mechanisms remain obscure and must be understood to permit rational manipulation and optimization of the technique. we set out to enhance the intracellular degradation of a viral antigen, with the intent of improving antigen entry into, and presentation by, the class i major histocompatibility complex pathway. we achieved this goal by cotranslational ubiquitination of ...	1997	9343207
agonist peptide modulates t cell selection thresholds through qualitative and quantitative shifts in cd8 co-receptor expression.	engagement of the tcr is a pivotal step in thymocyte development, ultimately resulting in the survival (positive selection) or loss (negative selection) of developing t cells. the roles of peptides and stromal cell interactions necessary for these selection events, however, are still poorly understood. to investigate the effects of agonist peptide in positive selection, we used a novel cell suspension model for in vitro thymic positive selection in adults. target thymocytes from h-2db-restricted ...	1997	9352358
distinct roles for lfa-1 and cd28 during activation of naive t cells: adhesion versus costimulation.	efficient t cell activation requires the engagement of a variety of ligand/receptor molecules in addition to t cell receptor (tcr)-major histocompatibility complex (mhc)/peptide interactions. the leukocyte function antigen 1 (lfa-1) and the cd28 glycoprotein have both been implicated in t cell activation. the present study dissects the roles of lfa-1 and cd28 in the activation of naive virus-specific cd8+ t cells. we demonstrate that lfa-1 facilitates t cell activation by lowering the amounts of ...	1997	9354475
1996 curt p. richter award. effects of viral infection on corticosterone secretion and glucocorticoid receptor binding in immune tissues.	during an immune challenge it has been suggested that responding cells secrete cytokines which then stimulate the release of glucocorticoids. glucocorticoids, in turn, are believed to bind to their receptors in target immune tissues and provide feedback inhibition on evolving immune responses. the foundations for this hypothesis have been drawn primarily from studies on animal models of autoimmune and/or inflammatory processes, and the relevance of these glucocorticoid-immune interactions to vir ...	1997	9364623
crucial role of marginal zone macrophages and marginal zone metallophils in the clearance of lymphocytic choriomeningitis virus infection.	macrophages play a key role in the immune defense against pathogens. they control early invasion by antigen-unspecific phagocytosis of pathogens and act as professional antigen-presenting cells to induce antigen-specific t cell responses. to investigate the involvement of particular subsets of the splenic macrophages in an antiviral immune response, we selectively depleted mice of splenic marginal zone macrophages (mzm) and marginal zone metallophils (mm) using the clodronate liposome depletion ...	1997	9368619
vaccination against persistent viral infection exacerbates cd4+ t-cell-mediated immunopathological disease.	lymphocytic choriomeningitis virus (lcmv) infection of normal mice results in a fatal immunopathologic meningitis mediated by cd8+ cytotoxic t lymphocytes (ctl). we have previously shown that female beta2-microglobulin-deficient (beta2m-/-) mice, which are also deficient in cd8+ t cells, are susceptible to lcmv-induced immune-mediated meningitis, characterized by significant weight loss and mortality. this lcmv disease in beta2m-/- mice is mediated by cd4+ t lymphocytes. our previous studies hav ...	1997	9371632
depletion of cd8+ t lymphocytes by murine monoclonal cd8 antibodies and restored specific t cell proliferation in vivo in a patient with chronic hepatitis c.	cellular immune mechanisms, especially those mediated by cd8+ t cells, are important in the pathogenesis and control of viral infections. on the other hand, as shown for chronic lymphocytic choriomeningitis virus infection in the mouse, cd8+ t cells may not only hinder the elimination of a virus, but make the host unresponsive to a second viral infection. in hepatitis c virus (hcv) infections, at least 50% of the patients become chronically infected, despite the detection of hcv-specific ctl and ...	1997	9378996
altered peptide ligands trigger perforin- rather than fas-dependent cell lysis.	ctls lyse fas-expressing target cells by the concomitant action of a perforin- and a fas-dependent mechanism. this study analyzed whether target cells pulsed with t cell antagonists and other altered peptide ligands (apls) were susceptible selectively to only one of these two mechanisms. in vivo and in vitro activated t cells from transgenic mice expressing a tcr specific for lymphocytic choriomeningitis virus were used as effector cells. to distinguish between perforin- and fas-dependent cytoto ...	1997	9379009