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serological evidence for antigenic variation in brains of mice infected persistently with the virus of lymphocytic choriomeningitis. 19807223186
in vitro generation of human cytotoxic lymphocytes by virus. viral glycoproteins induce nonspecific cell-mediated cytotoxicity without release of interferon.purified hemagglutinin and fusion glycoproteins of measles virus either in soluble form or inserted in artifical membranes bind to human peripheral blood lymphocytes and induce cell-mediated cytotoxicity (cmc) in a dose-response fashion. both autologous and heterologous noninfected target cells are lysed in vitro. the expression of cmc is not inhibited by anti-measles virus antibody added to lymphocytes previously exposed to viral glycoproteins. the killer lymphocytes are fc receptor positive, b ...19817276828
factors influencing specific antibody formation in mice persistently infected with lcm virus. 19817282173
biochemical composition of lymphocytic choriomeningitis virus interfering particles.lymphocytic choriomeningitis (lcm) was interfering particles were enriched relative to infectious virions by ultracentrifugation in a shallow gradient made of urografin. electrophoretic analysis revealed that they lacked the small ('s') 23s rna as well as gp-1 and gp-2 of the infectious virion and also lacked a newly characterized glycoprotein of apparent mol. wt. 85 x 10(3); instead, they contained a novel glycoprotein with mol. wt. 65 x 10(3).19817288413
correlation of glycosphingolipids and sialic acid in yac-1 lymphoma variants with their sensitivity to natural killer-cell-mediated lysis.sialoglycoconjugates and glycosphingolipids were quantitated in a series of variants derived from the yac-1 lymphoma, known to be highly sensitive to natural killer (nk)-cell-mediated lysis. the variants, which had widely diverging sensitivities to nk cells, were obtained by a number of methods, including selection in the presence of nk cells, antibody to h-2, or antibody to the murine leukemia-virus-induced antigen, and by fusion of sensitive cells with an nk-resistant cell line, a9ht. the sens ...19817309293
viral pathogenesis and resistance to defective interfering particles. 19807352005
agglutination of lymphocytic choriomeningitis virus-infected l cells by concanavalin a. 19807360057
virological and clinico-epidemiological considerations on the etiology of some encephalitides and other neurologic virus diseases. 19807376465
lymphocytic choriomeningitis virus-induced modification of catecholamine metabolism in developing rat brain. 19807402458
lymphomas associated with a tolerant lymphocytic choriomeningitis virus infection in mice.on each of 2 occasions when a tolerant lymphocytic choriomeningitis (lcm) virus infection was introduced experimentally by a natural route into breeding stock of the pirbright p(sd) mouse strain, and a comparison made with genetically identical controls, where was in successive generations an overall 15-fold increase in the incidence of lymphomas. most of these were recognized clinically after the age of 16 months. the same observation was made in mice of the p(h) strain from which the p(sd) str ...19807431820
formation and characterization of an intertypic lymphocytic choriomeningitis recombinant virus.an intertypic reassortant arenavirus has been obtained from co-infection of bhk-21 cells by two strains of lymphocytic choriomeningitis virus (lcm virus), we and armstrong (arm), having the large/small (l/s) viral rna genotype of we/arm. the two parental viruses have different virulence characteristics in hamsters and guniea-pigs. the reassortant virus induces lcm-we-type plaques in vero cell monolayers, but has the avirulent characteristics of lcm-arm in hamsters and two strains of guniea-pigs. ...19807463007
immunopathologic alterations of lymphatic tissues of mice infected with lymphocytic choriomeningitis virus. i. histopathologic findings.intraperitoneal infection with strain we lymphocytic choriomeningitis virus led to illness in all and death in a large proportion of colony-bred nmri mice. in their lymphoid organs, three distinct types of alterations could be distinguished: destruction of lymphocytes and mononuclear phagocytes, proliferation of lymphocytes, and fibrinoid necrosis of reticular cells and macrophages. after the intraperitoneal inoculation of 10(4) mouse infectious units, in the spleen, infectivity rapidly climbed ...19817464045
immunopathologic alterations of lymphatic tissues of mice infected with lymphocytic choriomeningitis virus. ii. pathogenetic mechanism. 19817464046
emergence of virus escape mutants after immunization with epitope vaccine.balb/c and c57bl/6j mice were immunized with recombinant vaccines consisting of lymphocytic choriomeningitis virus cd8+ t-lymphocyte epitopes and a carrier protein. during challenge infection with we strain lymphocytic choriomeningitis virus, mutants with alterations in distinct amino acid residues of the epitopic nonapeptides appeared and multiplied. splenocytes from we-infected balb/c mice lysed cells coated with the we-type epitope; lysis was considerably less effective when the epitopic nona ...19957474135
pathology and immunohistochemistry of callitrichid hepatitis, an emerging disease of captive new world primates caused by lymphocytic choriomeningitis virus.callitrichid hepatitis is an arenavirus infection that recently emerged as a highly fatal disease of new world primates in the callitrichidae family. as we previously reported, these primates develop hepatitis after contact with mice that are infected with variants of lcmv (lvmcch), recently determined to have 86% identity with gc-p gene of the armstrong and western strains of lcmv. here, we describe the histopathological lesions and tissue localization of viral antigens in confirmed cases of ca ...19957485406
efficient immune responses in mice lacking n-region diversity.mice with a null mutation in the terminal deoxynucleotidyl transferase (tdt) gene harbor immunoglobulin and t cell receptor repertoires essentially devoid of n-region diversity. consequently, the cdr3 loops important for antigen recognition are shorter and considerably less diverse than those of wild-type controls. we find surprisingly normal immune responses in tdt0 mice, as regards both efficiency and specificity. this provokes a reconsideration of the assumption that n-region diversity is req ...19957489751
oestrogen influences cd4+ t-lymphocyte activity in vivo and in vitro in beta 2-microglobulin-deficient mice.oestrogen directly influences autoimmune diseases and the immune response to microbes. we studied the effect of oestrogen on cd4+ t cells specific for lymphocytic choriomeningitis virus (lcmv) using mice genetically engineered to be deficient in beta 2-microglobulin (beta 2m-/-). these mice are deficient in beta 2-microglobulin, class i major histocompatibility complex (mhc) molecules and cd8+ t lymphocytes. fatal leptomeningitis after intracranial infection with lcmv is mediated by cd8+ cytotox ...19957490113
cell-mediated cytotoxicity in perforin-less mice.we have used a perforin-less (po) mouse to explore alternate ctl-mediated lytic pathways. po mice are unable to overcome an infection with lcmv in vivo. nevertheless, splenocytes from infected mice show vigorous, antigen-specific cytotoxicity that requires the presence of the fas antigen on target cells. the fas lytic pathway is virtually indistinguishable, in terms of kinetics and magnitude of cytotoxicity, from perforin/granzyme-mediated lysis. it is rapidly induced in ctl upon occupation of t ...19957494105
discriminated selection among viral peptides with the appropriate anchor residues: implications for the size of the cytotoxic t-lymphocyte repertoire and control of viral infection.structural characterization of peptides restricted by major histocompatibility complex (mhc) class i molecules has identified residues critical for mhc class i binding and for t-cell receptor recognition. for example, optimal peptides fitting into the murine mhc class i db groove are 9 to 11 amino acids long and require as mhc anchor residues an asn (n) at position 5 and also either a hydrophobic residue, a met (m) or a cys (c), at the carboxy terminus. the three known db-restricted peptides of ...19957494247
are hiv-specific ctl responses salutary or pathogenic?recently, hiv has been shown to be highly variable in patients; it is capable of escaping, or even turning off, cytotoxic t-cell responses by mutating t-cell epitopes. new antiviral drugs have revealed the enormous turnover of c4+ t cells in infected patients, but have also shown how efficiently hiv rapidly escapes such treatments. although hiv is usually considered to be cytopathic, this is not really known. the proposal that aids pathogenesis reflects immunopathological consequences of anti-hi ...19957495509
virus-activated t cells regulate expression of adhesion molecules on endothelial cells in sites of infection.to study the role of cell adhesion molecules in the fatal cd8+ t-cell mediated meningitis which is induced by intracerebral infection with lymphocytic choriomeningitis virus, the expression of relevant molecules on inflammatory cells and local endothelium was analyzed immunohistochemically. most inflammatory cells were strongly positive for lfa-1, vla-4, pgp-1 and icam-1. expression of icam-1 and vcam-1 was upregulated on the endothelial cells in immunocompetent mice, but not in t-cell deficient ...19957499490
endogenous il-2 contributes to t cell expansion and ifn-gamma production during lymphocytic choriomeningitis virus infection.il-2-deficient mice were used to examine the role of endogenous il-2 for supporting t cell proliferative responses during infection with lymphocytic choriomeningitis virus (lcmv). the studies showed that, although virus-specific ctl activity was induced in the absence of il-2, the overall magnitude of the response was profoundly inhibited. examination of proportions and numbers of cd8+ t cells demonstrated that the normal virus-induced expansion of these cells was virtually eliminated in spleens ...19957499855
t-cell receptors from virus-specific cytotoxic t lymphocytes recognizing a single immunodominant nine-amino-acid viral epitope show marked diversity.following infection of the h-2d mouse by lymphocytic choriomeningitis virus, the newly generated cytotoxic t lymphocyte (ctl) response is focused to a single 9-amino-acid peptide sequence (epitope) of the virus. more than 96% of the primary, secondary, and clonal ctl respond to this lymphocytic choriomeningitis virus nucleoprotein epitope. this unique system affords the opportunity to evaluate the t-cell response to a single viral ctl epitope in a case in which the outcome of infection, either v ...19947504738
changes in cell adhesion molecule expression on t cells associated with systemic virus infection.virus-induced changes in adhesion molecule expression on t cells were investigated to understand how antiviral effector cells migrate into infectious foci. facs analysis revealed that after systemic infection with lymphocytic choriomeningitis virus a number of cell adhesion molecules, including vla-4, lfa-1, and icam-1, are up-regulated on cd8+ cells, whereas the lymph node homing receptor mel-14 is down-regulated during the infection; only marginal changes were observed for cd4+ cells. basicall ...19947507962
mice expressing both b7-1 and viral glycoprotein on pancreatic beta cells along with glycoprotein-specific transgenic t cells develop diabetes due to a breakdown of t-lymphocyte unresponsiveness.t lymphocytes have been implicated in the onset of many autoimmune diseases; however, the mechanisms underlying t-cell activation toward self antigens are poorly understood. to study whether t-lymphocyte costimulation can overcome the immunologic unresponsiveness observed in an in vivo model, we have created transgenic mice expressing the costimulatory mouse molecule b7-1, a ligand for the cd28 receptor, on pancreatic beta cells. we now report that triple-transgenic mice expressing both b7-1 and ...19947512724
protection against lethal lymphocytic choriomeningitis virus (lcmv) infection by immunization of mice with an influenza virus containing an lcmv epitope recognized by cytotoxic t lymphocytes.the reverse genetics system has made it possible to modify the influenza virus genome. by this method, we were able to assess influenza virus as a vaccine vector for protecting balb/c mice against otherwise lethal lymphocytic choriomeningitis virus (lcmv) infection. a single dose of influenza virus [a/wsn/33 (h1n1)] bearing a cytotoxic t-lymphocyte-specific epitope of the lcmv nucleoprotein (residues 116 to 127) in the neuraminidase stalk protected mice against lcmv challenge for at least 4 mont ...19947514676
cytotoxic t-cell memory without antigen.memory is a hallmark of the immune system and ever since its recognition there has been considerable interest in understanding how immunity is maintained. the current model is that long-term memory is dependent on persistent antigenic stimulation. we report here results that challenge this view and provide evidence that antigen is not essential for the maintenance of cd8+ t-cell memory. we show that memory cd8+ cytotoxic t lymphocytes persist indefinitely in the absence of priming antigen, retai ...19947516038
fas and perforin pathways as major mechanisms of t cell-mediated cytotoxicity.two molecular mechanisms of t cell-mediated cytotoxicity, one perforin-based, the other fas-based, have been demonstrated. to determine the extent of their contribution to t cell-mediated cytotoxicity, a range of effector cells from normal control or perforin-deficient mice were tested against a panel of target cells with various levels of fas expression. all cytotoxicity observed was due to either of these mechanisms, and no third mechanism was detected. thus, the perforin- and fas-based mechan ...19947518614
mutations inside but not outside the peptide binding cleft of the h-2 ld molecule affect ctl recognition and binding of the nucleoprotein peptide from the lymphocytic choriomeningitis virus.in order to investigate the role of residues inside and outside the peptide binding cleft of the ld molecule in peptide presentation to cytotoxic t lymphocytes (ctl), we constructed a series of point mutations in the ld gene. we determined the effects of the mutations in the ld molecule on the binding and recognition of an ld-restricted ctl epitope derived from the nucleoprotein (np) of the lymphocytic choriomeningitis virus (lcmv). each of the mutations within the ld peptide binding cleft resul ...19947518804
cytolytic t-cell cytotoxicity is mediated through perforin and fas lytic pathways.the recent generation of perforin knock-out mice has demonstrated a crucial role for the pore-forming perforin in cytolytic t-lymphocyte (ctl)-mediated cytolysis. perforin-deficient mice failed to clear lymphocytic choriomeningitis virus in vivo, yet substantial killing activity still remained in perforin-free ctls in vitro, indicating the presence of (a) further lytic pathway(s). fas is an apoptosis-signalling receptor molecule on the surface of a number of different cells. here we report that ...19947520535
induction of protective immunity using minigenes. 19947521600
expression of the inducible nitric oxide synthase. correlation with neuropathology and clinical features in mice with lymphocytic choriomeningitis.nitric oxide (no) synthesized by the cytokine-inducible enzyme, nitric oxide synthase (inos), is thought to be a key mediator in the host immune response to infection, in which it may have protective, as well as injurious, actions. we sought evidence for a role of no in the pathogenesis of lymphocytic choriomeningitis by examining the cerebral expression of the inos gene in mice after intracranial inoculation of lymphocytic choriomeningitis virus. in euthymic, but not athymic, mice, elevated exp ...19947523499
thymic selection and adaptability of cytotoxic t lymphocyte responses in transgenic mice expressing a viral protein in the thymus.upon primary challenge with lymphocytic choriomeningitis virus (lcmv), h-2d (balb/cbyj) mice mount a cytotoxic t lymphocyte (ctl) response to a single immunodominant domain of the viral nucleoprotein (np) but no detectable response to the viral glycoprotein (gp). to manipulate this ctl response, the viral np gene was expressed in the thymus and peripheral t lymphocytes using the murine thy1.2 promoter. as a result, such thy1.2-np (h-2d) transgenic (tg) mice deleted their high-affinity anti-lcmv- ...19947525843
immune function in mice lacking the perforin gene.mice lacking the perforin gene were generated by using targeted gene disruption in embryonal stem cells. when infected with lymphocytic choriomeningitis virus (lcmv), perforin-less (-/-) mice showed clear signs of having mounted an immune response based on activation of cd8 t cells but were unable to clear the lcmv infection. this failure to eliminate virus was accompanied by a failure to generate spleen cells capable of lysing lcmv-infected fibroblasts in vitro. spleen cells from lcmv-infected ...19947526382
in vivo state of antiviral ctl precursors. characterization of a cycling cell population containing ctl precursors in immune mice.the in vivo state of cd8+ mouse memory ctl specific to lymphocytic choriomeningitis virus (lcmv) was characterized. during acute lcmv infection, the majority of the lcmv-specific ctl activity tested immediately ex vivo was mediated by cd8+ l-selectin- mac-1+ ctl. the l-selectin- population of cd8+ cells elicited during acute infection also carried > 99% of the restimulatable cd8+ ctl precursors (ctlp) to lcmv, and these required added il-2 for development into effectors in vitro. in contrast wit ...19957529281
nk cell response to viral infections in beta 2-microglobulin-deficient mice.because class i mhc ags have been implicated as modulators of target cell sensitivity to nk cell-mediated lysis, the regulation of virus infections and the fate of nk cells and their natural targets was examined in beta 2-microglobulin-deficient mice, which have defective class i mhc expression. infections with either the nk cell-sensitive murine cytomegalovirus (mcmv) or the nk cell-resistant lymphocytic choriomeningitis virus (lcmv) significantly augmented nk cell activity in either c57bl/6 (+ ...19957529286
role of virus and host variables in virus persistence or immunopathological disease caused by a non-cytolytic virus.c57bl/6 mice infected with increasing doses of the armstrong isolate of lymphocytic choriomeningitis virus (lcmv) or a variant cl 13-armstrong, derived from lcmv-armstrong, exhibited distinct phenotypes with respect to clearance of virus and to cytotoxic cd8+ t cell (ctl)-dependent immunopathological disease. low (10(2) p.f.u.) and high doses (10(7) p.f.u.) of lcmv-armstrong were cleared rapidly from immunocompetent mice. inoculation of a high dose (10(7) p.f.u.) of lcmv cl 13-armstrong temporar ...19957531218
immunobiology of cytotoxic t-cell escape mutants of lymphocytic choriomeningitis virus.infection with virus variants exhibiting changes in the peptide sequences defining immunodominant determinants that abolish recognition by antiviral cytotoxic t cells (ctl) presents a considerable challenge to the antiviral t-cell immune system and may enable some viruses to persist in hosts. the potential importance of such variants with respect to mechanisms of viral persistence and disease pathogenesis was assessed by infecting adult mice with variants of lymphocytic choriomeningitis virus (l ...19957533851
optimal lymphocytic choriomeningitis virus sequences restricted by h-2db major histocompatibility complex class i molecules and presented to cytotoxic t lymphocytes.infection with lymphocytic choriomeningitis virus induces the generation of cd8+ cytotoxic t lymphocytes (ctl). in the h-2b mouse, this cellular immune response is directed against three viral structural epitopes (gp1, gp2, and np) presented by the major histocompatibility complex (mhc) class i h-2db molecules. this study was undertaken to delineate which sequence of each of these three epitopes is optimal for mhc binding and ctl recognition. the first step was to synthesize the relevant peptide ...19957533855
antiviral protective immunity induced by major histocompatibility complex class i molecule-restricted viral t-lymphocyte epitopes inserted in various positions in immunologically self and nonself proteins.injection into mice of chimeric proteins consisting of a portion of either the simian virus 40 large tumor antigen or nonstructural protein 1 of influenza a virus or of the murine tumor suppressor p53 on one hand and t-cell epitopes of lymphocytic choriomeningitis virus on the other resulted in antiviral protective immunity, which was independent of the epitopes' position in the protein and the same whether the latter was immunologically nonself or self. mice of different haplotypes were protect ...19957533861
[virus-induced immune deficiency disease aids: direct pathogenic effect of the virus or immunopathology?].cytotoxic effectors-cd8+ t cells protect hosts against cytopathic viruses. cd8+ t cell mediated lysis of host cells infected with non-cytopathic viruses may lead to tissue disease causing damage as is the case in hepatitis b virus infections in men or lymphocytic choriomeningitis virus (lcmv) infections in mice. in a mouse model it was demonstrated that virus induced immunodeficiency by lcmv was not caused by the virus directly but rather by immunopathological consequences of anti-lcmv cd8+ t ce ...19947533980
[viral antigen induced autoimmunity: an animal model for diabetes mellitus type i].to address the mechanisms of tolerance to extrathymic proteins, we have generated transgenic mice expressing the lymphocytic choriomeningitis virus (lcmv) glycoprotein (gp) in the beta islet cells of the pancreas. the fate of lcmv-gp-specific t cells was followed by breeding the gp transgenic mice with t cell receptor transgenic mice, specific for lcmv-gp and h-2db. these studies suggest that "peripheral tolerance" of self-reactive t cells does not involve clonal deletion, clonal anergy, or a de ...19947533982
alpha 4 integrin directs virus-activated cd8+ t cells to sites of infection.this article examines the role of vla-4 in directing lymphocytes to sites of viral infection using the murine lymphocytic choriomeningitis virus infection (lcmv) as the model system. this virus by itself induces little or no inflammation, but in most mouse/virus strain combinations a potent t cell response is induced, which is associated with marked cd8+ cell-mediated inflammation. two expressions of lcmv-induced inflammation were studied: meningitis induced by intracerebral infection and adopti ...19957537304
t cell priming versus t cell tolerance induced by synthetic peptides.it is well known that synthetic peptides are able to both induce and tolerize t cells. we have examined the parameters leading either to priming or tolerance of cd8+ cytotoxic t lymphocytes (ctl) in vivo with a major histocompatibility complex class i (h-2 db) binding peptide derived from the glycoprotein (gp aa33-41) of lymphocytic choriomeningitis virus (lcmv). by varying dose, route, and frequency of lcmv gp peptide application, we found that a single local subcutaneous injection of 50-500 mi ...19957540654
molecular phylogeny of guanarito virus, an emerging arenavirus affecting humans.the nucleotide sequence of a portion of the nucleocapsid (n) gene of the guanarito virus prototype strain (inh-95551) has been determined. it was obtained by direct rna and polymerase chain reaction (pcr) fragment sequencing of the 3' end of the small (s) rna fragment. a comparison of this 782-nucleotide segment was done with the known homologous gene sequences of five other arenaviruses: junin, machupo, tacaribe, pichinde, and lymphocytic choriomeningitis (lcm). phylogenetic analysis of the n g ...19957542842
lymphocytic choriomeningitis virus infection is associated with long-standing perturbation of lfa-1 expression on cd8+ t cells.flow cytometric analysis of splenocytes from mice infected with lymphocytic choriomeningitis virus revealed marked and long-standing up-regulation of lfa-1 expression on cd8+, but not on cd4+ t cells. appearance of cd8+ t cells with a changed expression of adhesion molecules reflected polyclonal activation and expansion which was demonstrated not to depend on cd4+ t cells or their products. cell sorting experiments defined virus-specific ctl to be included in this population (lfa-1himel-14lo), b ...19957543210
alterations of a dominant epitope of lymphocytic choriomeningitis virus which affect class i binding and cytotoxic t cell recognition.we have investigated mutation of a dominant cytotoxic t cell (ctl) epitope from the nucleoprotein (np) of lymphocytic choriomeningitis virus (lcmv). five np peptide analogs with single substitutions at the predicted anchor residues (designated by the wild type amino acid, the position number and the new amino acid: p2a, p2r, m9l and m9k) and at a non-anchor position (s5n) were examined for binding to class i, h-2 ld molecules. each of the substitutions decreased or abolished the capacity of the ...19957544868
attenuated listeria monocytogenes as a live vector for induction of cd8+ t cells in vivo: a study with the nucleoprotein of the lymphocytic choriomeningitis virus.listeria monocytogenes spends most of its intracellular life cycle in the cytosol of the infected eucaryotic cells. within this cellular compartment originates the endogenous pathway of antigen processing and presentation. we thus assumed that recombinant l. monocytogenes expressing an heterologous protein, the nucleoprotein of the lymphocytic choriomeningitis virus (lcmv), should be able to induce antigen-specific cd8+ t cells in vivo. the lcmv nucleoprotein gene was inserted in phase with the ...19957547706
granzyme a-deficient mice retain potent cell-mediated cytotoxicity.granzyme a, a granule-associated serine proteinase of activated cytotoxic t cells and natural killer cells, has been reported to play a critical role in dna fragmentation of target cells. to address the question of the biological role of granzyme a, we have now generated a granzyme a-deficient mouse mutant by homologous recombination. western blot analysis, enzyme assays and reverse transcription-pcr confirmed the absence of granzyme a in activated t cells. in addition, deletion of granzyme a do ...19957556064
cell-invasive activity of epitope-tagged adenylate cyclase of bordetella pertussis allows in vitro presentation of a foreign epitope to cd8+ cytotoxic t cells.the adenylate cyclase (ac) toxin (cyaa) of bordetella pertussis has an invasive catalytic domain (ac domain) which penetrates the cytoplasmic membrane of a variety of eukaryotic cells and intoxicates them by unregulated synthesis of cyclic amp. previous work led to identification of five permissive sites in the ac domain at which heterologous peptides are accommodated without affecting its enzymatic properties. we have constructed a set of cyaa toxins tagged at these permissive sites by insertio ...19957558291
t cell development in cd8-/- mice. thymic positive selection is biased toward the helper phenotype.the cd4 and cd8 molecules are involved in t cell differentiation and activation. nevertheless, efficient thymic maturation of helper t cells has been shown in the absence of the cd4 molecule. these cd4-deficient helper t cells expressed alpha beta-tcr and were able to control leishmania infections and to mediate ab class switch. using mice deficient for the cd8 alpha-chain, we investigated whether a similar cytotoxic t cell population was generated in the absence of the cd8 coreceptor. a cd8-def ...19957561076
circulating intercellular adhesion molecule-1 (icam-1) as an early and sensitive marker for virus-induced t cell activation.the effect of systemic virus infection on the level of circulating icam-1 (cicam-1) in serum, and the role of virus-activated t cells in this context, were studied using the murine lymphocytic choriomeningitis virus infection as primary model system. a marked virus-induced elevation in cicam-1 in serum was revealed, the presence of which coincided with the phase of virus-induced t cell activation. however, high levels of cicam-1 in serum were observed well before maximal t cell activation could ...19957586677
principles of cytotoxic t lymphocyte induction and recognition. 19957587366
virus-neuron-cytotoxic t lymphocyte interactions. 19957587367
clonal deletion of major histocompatibility complex class i-restricted cd4+cd8+ thymocytes in vitro is independent of the cd95 (apo-1/fas) ligand.the cd95 (apo-1/fas) ligand (cd95l) mediates apoptosis in sensitive target cells, ca(2+)-independent cytotoxicity of cells from perforin knock-out mice, and peripheral deletion of activated t cells through engagement of its cognate receptor cd95. double-positive thymocytes show a high constitutive expression of cd95. therefore, we used a model system and investigated whether negative selection through apoptosis might involve cd95/cd95l. we analyzed whether cd95l may induce antigen-specific delet ...19957589104
t cell development and repertoire of mice expressing a single t cell receptor alpha chain.we examined t cell development and t cell repertoire in transgenic mice expressing a single t cell receptor (tcr) alpha chain derived from the h-2db-lymphocytic choriomeningitis virus (lcmv)-specific cytolytic t lymphocyte (ctl) clone p14. to generate these alpha p14 mice, mice transgenic for the p14 tcr alpha chain were backcrossed to tcr alpha-deficient mice. thymi from alpha p14 mice exhibited a marked decrease of mature cd4+8- and cd8+4- single-positive thymocytes comparable to thymi from tc ...19957589140
prevention of autoimmune disease by retroviral-mediated gene therapy.t lymphocytes have been implicated in a variety of autoimmune diseases, and therefore one potential therapeutic approach would be to tolerize the pathogenic self-reactive t cells. in this study, we examined whether retroviral gene therapy could be used to induce tolerance and prevent autoimmunity using a transgenic mouse model for experimentally induced diabetes. in this model, the lymphocytic choriomeningitis virus (lcmv) glycoprotein (gp) is expressed on the beta-islet cells of the pancreas un ...19957594557
consequences of cytotoxic t lymphocyte interaction with major histocompatibility complex class i-expressing neurons in vivo.neurons have evolved strategies to evade immune surveillance that include an inability to synthesize the heavy chain of the class i major histocompatibility complex (mhc), proteins that are necessary for cytotoxic t lymphocyte (ctl) recognition of target cells. multiple viruses have taken advantage of the lack of ctl-mediated recognition and killing of neurons by establishing persistent neuronal infections and thereby escaping attack by antiviral ctl. we have expressed a class i mhc molecule (db ...19957595191
strictly transporter of antigen presentation (tap)-dependent presentation of an immunodominant cytotoxic t lymphocyte epitope in the signal sequence of a virus protein.peptides presented by major histocompatibility complex (mhc) class i molecules are derived from intracellularly synthesized proteins. cytosolic proteins are fragmented into peptides, which are subsequently transported via the transporter of antigen presentation (tap) into the endoplasmic reticulum (er), where they bind to mhc class i molecules. we have investigated the requirements for mhc class i presentation of the immunodominant gp33 cytotoxic t lymphocyte epitope of the lymphocytic choriomen ...19957595234
lymphocyte apoptosis during the silencing of the immune response to acute viral infections in normal, lpr, and bcl-2-transgenic mice.this report examines the mechanisms involved in the down-regulation of the immune response in acute viral infection and documents the presence of apoptotic lymphocytes in situ in the spleens of mice during the resolution of the immune response to acute lymphocytic choriomeningitis virus infection. apoptotic cells were detected by an in situ nucleotidyl transferase assay. both t and b lymphocytes were shown to be dying in vivo, the latter in clusters. a biphasic occurrence of apoptosis during the ...19957604887
antiviral defense in mice lacking both alpha/beta and gamma interferon receptors.alpha/beta interferon (ifn) and gamma ifn exert widely overlapping biological effects. still, mice with individually inactivated alpha/beta or gamma receptors exhibit variably severely reduced resistance to infection and altered immune responses. to investigate to what extent the two ifn systems are functionally redundant, we generated mice with a combined receptor defect (ag129 mice). like mice with individual mutations, ag129 mice had no apparent anomalies, confirming that in the mouse the ifn ...19957609046
antiviral immune responses in mice deficient for both interleukin-2 and interleukin-4.antiviral immune responses of mice lacking interleukin-2 (il-2) or il-4 or both il-2 and il-4 (il-2/4) were compared by using different viruses. primary cytotoxic t-lymphocyte (ctl) responses against lymphocytic choriomeningitis virus (lcmv) were only moderately reduced in mice lacking il-2 and were normal in mice lacking il-4. mice deficient in both interleukins exhibited variable and more strongly reduced but nevertheless in vivo protective lcmv-specific ctl responses. similar results were obt ...19957609051
tap1-independent loading of class i molecules by exogenous viral proteins.presentation of peptides derived from endogenous proteins on class i molecules needs functional tap peptide transporters. to reveal whether class i-associated presentation of exogenous proteins also required the presence of tap transporters, we assessed in vitro the ability of spleen cells and macrophages from tap1-deficient mice (tap1-/-) to present peptides derived from exogenous recombinant viral proteins on their class i molecules. we found that recombinant glyco- and nucleoprotein from lymp ...19957615001
ctl escape viral variants. ii. biologic activity in vivo.the proteins of lymphocytic choriomeningitis virus (lcmv) contain only three known peptide regions that are processed and then held in place by the mhc class i h-2b (db) glycoprotein on the cell's surface for recognition by lcmv-specific db-restricted cytotoxic t lymphocytes (ctl). these peptides are from the glycoprotein (gp), amino acids 33-41 kavynfatc (gp1) and 276-286 sgvenpggycl (gp2), and the nucleoprotein (np), 396-404. we have used ctl clones that recognized only gp1, gp2, and np to sel ...19957645248
toxicity and carcinogenicity of 2,3-dibromo-1-propanol in f344/n rats and b6c3f1 mice.2,3-dibromo-1-propanol is a metabolite of the flame retardant tris(2,3-dibromopropyl) phosphate, previously shown to be a mutagen and carcinogen in experimental animals. toxicology and carcinogenesis studies of 2,3-dibromo-1-propanol were conducted by applying the chemical in 95% ethanol to the interscapular skin of male and female f344/n rats and b6c3f1 mice 5 days a week for 13 weeks in the prechronic study and 48-55 weeks (rats) or 36-42 weeks (mice) in the carcinogenicity study. in the 13-we ...19957657061
an essential role for type 1 interferon-gamma in terminating persistent viral infection.the mechanism(s) by which infectious material is cleared by the host is an area of intensive study. this is especially so with the realization that persistent viral infection is a cause of chronic disease in humans and presents a major health problem. we have used the murine model of infection with lymphocytic choriomeningitis virus to evaluate immune clearance. mice with a targeted disruption of the ifn-gamma gene mount effective cytotoxic t lymphocyte (ctl) responses after an acute viral chall ...19957676639
concurrent sequence analysis of 5' and 3' rna termini by intramolecular circularization reveals 5' nontemplated bases and 3' terminal heterogeneity for lymphocytic choriomeningitis virus mrnas.we have used a technique of rna circularization coupled with polymerase chain reaction amplification for simultaneous analysis of the 5' and 3' termini of subgenomic mrnas derived from the s rna of lymphocytic choriomeningitis virus during an acute infection of bhk cells. these mrnas possess 1 to 7 nontemplated nucleotides of apparently random sequence at their 5' ends. the predominant mrna species have 4 or 5 nontemplated nucleotides. the 5' termini of the mrnas also have properties consistent ...19937682625
virus and cytotoxic t lymphocytes: crucial role of viral peptide secondary structure in major histocompatibility complex class i interactions.viral antigens are presented to cytotoxic t lymphocytes (ctls) by h-2-restricted major histocompatibility complex (mhc) glycoproteins. binding of the endogenously processed viral peptides (epitopes) to their specific mhc molecules is an early intracellular event in the recognition process and is necessary for subsequent killing of virus-infected cells by virus-specific ctls. it is now well established that interaction between a viral antigenic peptide and mhc is dependent on the primary structur ...19937682632
virus-specific cytotoxic t cell-mediated lysis of lymphocytes in vitro and in vivo.virus-specific ctl play a major role in early antiviral protection against lymphocytic choriomeningitis virus (lcmv). when mice are infected with high doses of certain lcmv isolates, the initiated ctl response may vanish before the virus is eliminated completely. to evaluate the possibility that this may be because of ctl lysing ctl, we studied the susceptibility to lysis of lcmv-specific ctl clones and of primary immune spleen cells in vitro and in vivo. confirming earlier reports, ctl were lys ...19937684417
cross-protection against lymphocytic choriomeningitis virus mediated by a cd4+ t-cell clone specific for an envelope glycoprotein epitope of lassa virus.recombinant vaccinia virus expressing the lassa virus (lv) envelope glycoprotein precursor, v-lsgpc, was used to study the basis of lv-induced cross-protective immunity against the closely related arenavirus lymphocytic choriomeningitis virus (lcmv). c3h/hej mice primed with v-lsgpc developed neither circulating antibodies nor cd8+ cytotoxic t cells specific for lcmv, yet they resisted a normally lethal lcmv challenge. spleen cells from such mice gave a proliferative response to lcmv in vitro th ...19937684468
altered cytokine genes expression by cona-activated spleen cells from mice infected by lymphocytic choriomeningitis virus.the intravenous injection of mice with lymphocytic choriomeningitis virus (lcmv) induces a rapid and long-lasting immunodeficiency. t lymphocytes from 7-day-infected mice do not proliferate in vitro in response to cona stimulation, do not produce il-2 but display high affinity il-2 receptors on their membrane. the non-coordinated regulation of these genes suggested that other cytokine-encoding genes may also be affected in their regulation. we have thus analyzed the expression of the genes encod ...19937685735
[milestones in virology].the "milestones" of virology try to depict the development from variolation to construction of hybrid viruses. not only single observations or detections are listed, in contrast, this is an attempt to delineate from single events conclusions for the more general development of virology. because of the increase of specialization in experimental sciences, it is often difficult for researchers to realize the roots of their present problems. often, earlier conclusions are being overlooked, from whic ...19937687580
differential t cell costimulatory requirements in cd28-deficient mice.t cell receptor stimulation without costimulation is insufficient for the induction of an optimal immune response. it is thought that engagement of the cd28 molecule with its ligand b7 provides an essential costimulatory signal without which full activation of t cells cannot occur. a mouse strain with a defective cd28 gene was established. development of t and b cells in the cd28-deficient mice appeared normal. however, t lymphocytes derived from cd28-/- mutant mice had impaired responses to lec ...19937688139
impairment and delay of neutralizing antiviral antibody responses by virus-specific cytotoxic t cells.after infection with some viruses that tend to persist, neutralizing antibodies are generated rather late, i.e., after 1 to 3 mo. this has been observed for hiv, hepatitis b infection in man, or after infection with lymphocytic choriomeningitis virus (lcmv) in mice. in contrast, nonneutralizing antibodies to lcmv are generated by day 7 and reach high titers by day 10. this study attempts to evaluate reasons for late and low titered neutralizing antibody responses. after a primary infection with ...19937693811
molecular determinants of macrophage tropism and viral persistence: importance of single amino acid changes in the polymerase and glycoprotein of lymphocytic choriomeningitis virus.this study documents that the immunosuppressive lymphocytic choriomeningitis virus (lcmv) variant, clone 13, shows a specific predilection for enhanced infection of macrophages both in vitro and in vivo and that single amino acid changes in the viral polymerase and glycoprotein are responsible for macrophage tropism. the growth difference seen between variant clone 13 and the parental armstrong strain was specific for macrophages, since both clone 13 and armstrong grew equally well in fibroblast ...19937693969
protective ctl-dependent immunity and enhanced immunopathology in mice immunized by particle bombardment with dna encoding an internal virion protein.anti-viral ctl were induced in vitro using a particle bombardment device or "gene-gun" to deliver plasmid dna encoding the nucleoprotein of the lymphocytic choriomeningitis virus (lcmv). using this plasmid we were able to study t cell-mediated immunity in the absence of a neutralizing ab response. upon a single dna immunization, a nearly 2 log10 reduction in splenic viral titers was observed 3 days after lcmv infection. after two or three immunizations a greater than 3 log10 inhibition of viral ...19957706740
attenuated mengo virus: a new vector for live recombinant vaccines.several features make mengo virus an excellent candidate for use as a vaccine vector. the virus has a wide host range, including rodents, pigs, monkeys, and most likely humans, and expresses its genome exclusively in the cytoplasm of the infected cell. stable attenuated strains exist which are deleted for part of the 5' noncoding region of the genome. here we report an attenuated mengo virus recombinant, vlcmg4, that encodes an immunodominant cytotoxic t-lymphocyte epitope of the lymphocytic cho ...19957707549
5' termini of pichinde arenavirus s rnas and mrnas contain nontemplated nucleotides.primer extension of pichinde arenavirus purified virion rna suggests that genomes have at least a single nontemplated base at the 5' end which is a g in all cdna clones having one such single base. on the other hand, the predominant products of primer extension on total virus-infected-cell rna are at positions -1 and -2. the primer extension product at position -2 is not represented in virion rna, and neither of these products is proportionally represented in mrna. mrna is predominantly 3 or 4 b ...19957707553
peptides control the gain and loss of allele specificity by mutated mhc class i molecules.to analyze the molecular basis of mhc class i allele-restricted peptide recognition, a set of eight ld/lq mutants was constructed and tested for peptide recognition by allele-restricted and peptide-specific ctl. the mhc molecules h-2ld and h-2lq differ at six amino acid positions (95, 97, 107, 116, 155, 157) located within the alpha 2 domain of the molecule. both molecules present the lymphocytic choriomeningitis virus (lcmv) nucleoprotein-derived peptide rpqasgvym and the murine cytomegalovirus ...19957722309
recombinant listeria monocytogenes as a live vaccine vehicle for the induction of protective anti-viral cell-mediated immunity.listeria monocytogenes (lm) is a gram-positive bacterium that is able to enter host cells, escape from the endocytic vesicle, multiply within the cytoplasm, and spread directly from cell to cell without encountering the extracellular milieu. the ability of lm to gain access to the host cell cytosol allows proteins secreted by the bacterium to efficiently enter the pathway for major histocompatibility complex class i antigen processing and presentation. we have established a genetic system for ex ...19957732018
murine hepatitis caused by lymphocytic choriomeningitis virus. ii. cells involved in pathogenesis.human virus hepatitides are often assumed to result from pathogenic immune responses rather than from direct viral cytopathic effects, but the details are largely unknown. hepatitis of the mouse undergoing infection with lymphocytic choriomeningitis (lcm) virus is an immunopathologic phenomenon, and its analysis may help us to understand some of the events leading to the human illnesses.19957745950
kinetics and ph dependence of acid-induced structural changes in the lymphocytic choriomeningitis virus glycoprotein complex.the nbd-pe/rd-pe fluorescent membrane fusion assay was used to measure the ph dependence and kinetics of the fusion activity of lymphocytic choriomeningitis virus with liposomes designed to mimic the composition of the endosomal membrane. fusion activity was only observed at ph values less than 6.3 and showed a greater rate and extent at lower ph values. pronounced kinetic fusion curves were observed at ph values below 5.8. when equivalent lipid amounts of target liposomes and virus were mixed a ...19957747483
fibroblasts as efficient antigen-presenting cells in lymphoid organs.only so-called "professional" antigen-presenting cells (apcs) of hematopoietic origin are believed capable of inducing t lymphocyte responses. however, fibroblasts transfected with viral proteins directly induced antiviral cytotoxic t lymphocyte responses in vivo, without involvement of host apcs. fibroblasts induced t cells only in the milieu of lymphoid organs. thus, antigen localization affects self-nonself discrimination and cell-based vaccine strategies.19957761853
ctl escape viral variants. i. generation and molecular characterization.cytotoxic t lymphocytes (ctl) play a pivotal role in preventing persistent viral infections and aborting acute infections. h-2db-restricted ctl optimally recognize a specific peptide of 9 to 11 amino acids (aa) derived from a viral protein and held in place (restricted) by a mhc class i glycoprotein on the surfaces of infected cells. only three peptide sequences with the appropriate db motif from lymphocytic choriomeningitis virus armstrong strain (lcmv) are known to be presented to ctl by h-2db ...19957793078
meningitis due to lymphocytic choriomeningitis virus: four cases in france. 19957795066
t lymphocyte-mediated antiviral immune responses in mice are diminished by treatment with monoclonal antibody directed against the interleukin-2 receptor.blocking the interleukin-2 receptor's alpha-chain in lymphocytic choriomeningitis virus-infected mice by treatment with monoclonal antibodies diminished the increase of numbers of cd8+ t lymphocytes in spleens and prevented cd8+ t lymphocyte-mediated virus clearance from organs as well as generation of virus-specific cytotoxic t lymphocytes. also, the cd8+ t cell-mediated early phase of the delayed-type hypersensitivity footpad swelling reaction was decreased. the same treatment had no effect on ...19947805738
virus-induced immunosuppression: immune system-mediated destruction of virus-infected dendritic cells results in generalized immune suppression.despite the clinical importance of virus-induced immunosuppression, how virus infection may lead to a generalized suppression of the host immune response is poorly understood. to elucidate the principles involved, we analyzed the mechanism by which a lymphocytic choriomeningitis virus (lcmv) variant produces a generalized immune suppression in its natural host, the mouse. whereas adult mice inoculated intravenously with lcmv armstrong rapidly clear the infection and remain immunocompetent, inocu ...19957815484
cdna sequence analysis confirms that the etiologic agent of callitrichid hepatitis is lymphocytic choriomeningitis virus.callitrichid hepatitis is an infection of new world primates caused by an arenavirus, currently referred to as callitrichid hepatitis virus, that is closely related to lymphocytic choriomeningitis virus (lcmv). we have cloned and sequenced the gp-c gene of callitrichid hepatitis virus and found that the cdna sequence is 84 to 86% identical to those of the gp-c genes of lcmv strains armstrong and we, while the deduced amino acid sequence is 95 to 96% identical to those of the gp-c gene products o ...19957815520
antiviral activity of nk 1.1+ natural killer cells in c57bl/6 scid mice infected with murine cytomegalovirus.the activation, proliferation, and antiviral effects of natural killer (nk) cells were examined in a newly developed stock of mice, c57bl/6jsz mice homozygous for the severe combined immunodeficiency (scid) mutation. these mice lack functional t and b cells and express the nk 1.1 alloantigen. such nk 1.1 expression facilitates the analysis of nk cells and their depletion in vivo with a monoclonal anti-nk 1.1 antibody. these mice, therefore, provide an excellent model to examine unambiguously the ...19947833623
origin of lymphocytic-choriomeningitis-virus-bearing mice in japan.mice found in the port areas in japan, where antibody to lymphocytic choriomeningitis virus (lcmv) was detected, may have originated or partially originated from a southern asian subspecies, mus musculus castaneus.19947839750
involvement of cd4+ cells in lymphocytic choriomeningitis virus-induced autoimmune anaemia and hypergammaglobulinaemia.development of pathology varies widely between different strains of mice after intracerebral inoculation with the so-called 'docile' isolate of lymphocytic choriomeningitis (lcm) virus. the c3heb/fej and b10. br/sgsnj mouse strains have been of special interest because they display autoimmune haemolytic anaemia with varying degrees of apparent immunological involvement. in this report, we examined the role of cd4+ t helper cells in this autoimmune response by treating mice with the cd4-specific ...19947840852
bone marrow is a major site of long-term antibody production after acute viral infection.antiviral antibody production is often sustained for long periods after resolution of an acute viral infection. despite extensive documentation of this phenomenon, the mechanisms involved in maintaining long-term antibody production remain poorly defined. as a first step towards understanding the nature of long-term humoral immunity, we examined the anatomical location of antibody-producing cells during acute viral infection. using the lymphocytic choriomeningitis virus (lcmv) model, we found th ...19957853531
risk of infections transmitted by arthropods and rodents in forestry workers.one hundred and fifty-one forestry workers and 151 matched office clerks were compared as to the presence of antibodies against borelia burgdorferi, tick-borne encephalitis virus, puumalavirus and lymphocytic choriomeningitis virus. their occupational risks of being infected by borrelia was fourfold and significant, by puumalavirus and lymphocytic choriomeningitis virus was increased but not significant. no seropositivity has been established against tick-borne encephalitis virus.19947859849
focal expression of interleukin-2 does not break unresponsiveness to "self" (viral) antigen expressed in beta cells but enhances development of autoimmune disease (diabetes) after initiation of an anti-self immune response.the participation of il-2 in insulin-dependent (type 1) diabetes (iddm) was analyzed in transgenic (tg) mice expressing the nucleoprotein (np) of lymphocytic choriomeningitis virus and il-2 under control of the rat insulin promoter focally in beta cells of the islets of langerhans. insertion and expression of the viral (self) gene or of the il-2 gene alone did not lead to iddm. infiltration primarily of cd4 and b lymphocytes and increased expression of mhc class i and ii molecules occurred in is ...19957860729
sensitization to self (virus) antigen by in situ expression of murine interferon-gamma.autoimmune disease results from inflammatory destruction of tissues by aberrant self-reactive lymphocytes. we studied the autoimmune potential of t lymphocytes immunologically ignorant of viral antigens acting as self antigens and whether the host defense molecule ifn-gamma could stimulate these cells to cytotoxic competency. for this purpose, we produced double transgenic mice expressing pancreatic ifn-gamma as well as lymphocytic choriomeningitis virus (lcmv) nucleoprotein (np) or glycoprotein ...19957860730
virus-specific cd8+ cells can switch to interleukin 5 production and induce airway eosinophilia.virus infections of the lung are thought to predispose individuals to asthma, a disease characterized by eosinophil infiltration of the airways. cd8+ t cells are an important part of the host response to virus infection, however, they have no reported role in eosinophil recruitment. we developed a mouse model of virus peptide-stimulated cd8+ t cell immune responses in the lung. we found that bystander cd4+ t helper cell type 2 immune responses to ovalbumin switched the virus peptide-specific cd8 ...19957869040
mechanism of interleukin 12-mediated toxicities during experimental viral infections: role of tumor necrosis factor and glucocorticoids.interleukin 12 (il-12) doses in excess of 100 ng/d have been shown to induce profound immunotoxicities in mice infected with lymphocytic choriomeningitis virus (lcmv). these immunotoxicities are characterized by almost complete inhibition of virus-induced cd8+ t cell expansion and ctl activation, and up to 2 log increases in viral replication. they are accompanied by induction of serum tumor necrosis factor (tnf). the studies presented here were undertaken to characterize mechanisms for the il-1 ...19957869050
immunological function of a defined t-cell population tolerized to low-affinity self antigens.in the thymus there are two major mechanisms of t-lymphocyte tolerance: clonal deletion and clonal inactivation. one important problem underlying the mechanism of clonal inactivation is why unresponsive cells are maintained in the mature peripheral t-cell repertoire. here we report that transgenic alpha beta t-cells may be tolerized to a self antigen mls-1a, but still retain proliferative responses for alternative peptide antigens and superantigens. these self-tolerant t cells can also provide i ...19957870174
dna vaccination against persistent viral infection.this study shows that dna vaccination can confer protection against a persistent viral infection by priming cd8+ cytotoxic t lymphocytes (ctl). adult balb/c (h-2d) mice were injected intramuscularly with a plasmid expressing the nucleoprotein (np) gene of lymphocytic choriomeningitis virus (lcmv) under the control of the cytomegalovirus promoter. the lcmv np contains the immunodominant ctl epitope (amino acids 118 to 126) recognized by mice of the h-2d haplotype. after three injections with 200 ...19957884908
dna immunization confers protection against lethal lymphocytic choriomeningitis virus infection.dna vaccination has been evaluated with the lymphocytic choriomeningitis virus (lcmv) model system. plasmid dna encoding the lcmv nucleoprotein, when injected intramuscularly, induces both antiviral antibodies and cytotoxic t lymphocytes. injection of dna encoding the nucleoprotein or the viral glycoprotein confers protection against normally lethal lcmv challenge in a major histocompatibility complex-dependent manner. the protection conferred is incomplete, but it is most probably mediated by t ...19957884923
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