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[serological study of the incidence of murine viruses in a population of small wild rodents (microtus pennsylvanicus ord, 1815)].the results of a serological survey of a free-living population of meadow voles (microtus pennsylvanicus) in pinawa, manitoba (canada) showed that these animals possessed antibodies to six of the eleven viruses tested for, namely: reovirus type 3, murine encephalomyelitis agent, ectromelia virus, murine adenovirus, murine hepatitis virus and lymphocytic choriomeningitis virus. the significant increase in the number of individuals possessing specific antibodies suggests that these viruses, or rel ...19921339064
induction and prevention of type 1 diabetes mellitus by viruses.genetic factors and environmental factors are thought to be involved in the pathogenesis of insulin-dependent diabetes mellitus type 1. viruses, as one environmental factor, may act as primary injurious agents to beta cells or as triggering agents for autoimmunity. some viruses such as emc-d and coxsackie b4 can induce type 1 diabetes by infecting and destroying beta cells in genetically susceptible mice. in addition, certain species of monkey, such as patas, show elevated blood glucose levels a ...19921292946
novel lcmv-specific h-2k restricted ctl clones recognize internal viral gene products and cause cns disease.h-2k (c3h/hej) cytotoxic t lymphocytes (ctl) specific for lymphocytic choriomeningitis virus (lcmv) were cloned. three clones recognizing internal viral antigens were studied. one such ctl clone recognized neither the glycoprotein nor nucleoprotein encoded by the viral short rna segment, but reacted with a protein encoded by the long rna segment, either the viral polymerase, or the z protein. this one clone, in addition to primary ctl harvested from immunized c3h mice, failed to lyse target cell ...19921281166
autoimmunity--towards the year 2001.the interactive roles of t cells, major histocompatibility complex (mhc) class i and ii molecules and antigen-presenting cells in the generation of autoimmunity is the subject of much discussion. a recent symposium contributed to the debate by inviting experts in several fields of immunology to answer specific questions relating to the mechanisms that trigger autoimmunity.19921356343
elisa and indirect immunofluorescence in the diagnosis of lcm virus infections.thirty-seven matched samples of patient sera with the clinical diagnosis of a lymphocytic choriomeningitis (lcm) infection, as well as 56 matched samples of patient sera with the clinical diagnosis of a cns infection of vague etiology were examined. two serological techniques, indirect immunofluorescence (if) and elisa were used. they revealed 16.2% of positive sera confirming the clinical diagnosis of the disease; in the cases of clinical diagnosis of cns infection of vague etiology 8.9% of pos ...19921363992
vaccination with a synthetic peptide modulates lymphocytic choriomeningitis virus-mediated immunopathology.vaccination with a nucleopeptide (np 118; amino acids 118 to 132) representing a cytotoxic t-cell epitope of lymphocytic choriomeningitis virus (lcmv) can modulate immunopathology. immunization with np 118 protected h-2d mice against intracerebral infection with the lcmv-armstrong isolate. however, when np 118-primed h-2d mice were challenged intracerebrally with an intermediate dose (5 x 10(4) pfu) of the lcmv-docile strain, all mice primed with np 118 emulsified in incomplete freund's adjuvant ...19921370548
diversity of t-cell receptors in virus-specific cytotoxic t lymphocytes recognizing three distinct viral epitopes restricted by a single major histocompatibility complex molecule.cytotoxic t lymphocytes (ctl) recognize virus peptide fragments complexed with class i major histocompatibility complex (mhc) molecules on the surface of virus-infected cells. recognition is mediated by a membrane-bound t-cell receptor (tcr) composed of alpha and beta chains. studies of the ctl response to lymphocytic choriomeningitis virus (lcmv) in h-2b mice have revealed that three distinct viral epitopes are recognized by ctl of the h-2b haplotype and that all of the three epitopes are restr ...19921372370
a common antiviral cytotoxic t-lymphocyte epitope for diverse major histocompatibility complex haplotypes: implications for vaccination.of nine established murine haplotypes, mice of three types (h-2d, h-2u, and h-2q) possess major histocompatibility complex class i glycoproteins able to present an identical viral peptide for recognition and lysis by virus-specific cytotoxic t lymphocytes. incorporation of this viral epitope into a recombinant vaccinia vaccine and administration of a single dose protects mice with these three haplotypes from an ordinarily lethal challenge of virus. hence, a common epitope can exist. the sharing ...19921372990
mechanisms of antibody-mediated protection against lymphocytic choriomeningitis virus infection: mother-to-baby transfer of humoral protection.the role of antiviral antibodies in resistance to lymphocytic choriomeningitis virus (lcmv) infection was explored. immune serum and monoclonal antibodies prevented fatal t-cell-mediated immunopathology following acute lcmv infections. in addition, 10- and 14-day-old mice that received maternally derived anti-lcmv antibodies through nursing were protected from an otherwise lethal lcmv challenge. detailed investigation of the mechanism(s) by which these antiviral antibodies provided was carried o ...19921376367
design of high-affinity major histocompatibility complex-specific antagonist peptides that inhibit cytotoxic t-lymphocyte activity: implications for control of viral disease.cytotoxic t lymphocytes (ctls) recognize viral antigens presented by infected cells in the context of their major histocompatibility complex glycoproteins. the irreversible killing of virus-infected cells by virus-specific ctls can be the cause of serious disease, particularly in the central nervous, hepatic, and cardiovascular systems. design of molecules controlling (blocking) interaction between ctls and infected cells, and their further use to inhibit (or antagonize) t-lymphocyte activity, i ...19921383569
control of acute infection with lymphocytic choriomeningitis virus in mice that cannot present an immunodominant viral cytotoxic t lymphocyte epitope.for controlling infection of the mouse with the lymphocytic choriomeningitis (lcm) virus, cd8+ ctl are essential. in the infected balb/c mouse the arising lcm virus-specific ctl are exclusively restricted by the class i mhc-encoded molecule l; k- or d-restricted antiviral ctl cannot be detected. thus, the infected l-deficient balb/c mutant c-h-2dm2 should not be capable of eliminating the virus. the experimental evidence proves the contrary, which is explained by k- and d-restricted ctl that thi ...19921385522
analysis of immature (cd4-cd8-) thymic subsets in t-cell receptor alpha beta transgenic mice.introduction of a transgenic alpha beta tcr (v alpha 2, v beta 8.1) specific for lymphocytic choriomeningitis virus (lcmv), in the context of h-2db into the genome of c57bl/6 mice, has many effects on the development and selection of t cells in both the thymus and the periphery. these mice produce increased numbers of cd4-8+ mature t cells, all of which express the transgenic tcr, and small numbers of cd4+8- cells using endogenous tcrs are also produced. this study follows the intrathymic develo ...19921386545
kinetics of clonal deletion varies with tolerizing antigen.in postnatal akr/j mice (i-ek, mls-1a) potentially autoreactive t-cells bearing v beta 11+ or v beta 6+ tcr are present until day 4, rapidly decreasing thereafter. clonal deletion of v beta 11+ and v beta 6+ t-cells shows equivalent kinetics and is complete after day 7 to 8. analysis of transgenic mice expressing a tcr with double specificity for lcmv/h-2db and for mls-1a revealed that in mice congenically infected with lymphocytic choriomeningitis virus (lcmv) t-cells bearing the transgenic tcr ...19921387745
virally induced immunosuppression.a mouse model of virus-triggered, t-cell mediated acquired immunosuppression is analyzed. lymphocytic choriomeningitis virus initially infects mostly macrophages and antigen-presenting cells; these are destroyed by lymphocytic choriomeningitis virus specific cytotoxic t cells resulting in immunosuppression. similar immunopathological mechanisms may play a role in acquired immune deficiency syndrome.19921388842
thymocytes can tolerize thymocytes by clonal deletion in vitro.clonal deletion of thymocytes bearing tcr for self antigens is one major mechanism of t cell tolerance induction. peptide antigen-induced deletion of thymocytes from alpha beta tcr transgenic mice has been studied using single cell suspension cultures. the results show that antigen-presenting immature cd4+cd8+ thymocytes can tolerize antigen-reactive immature thymocytes in vitro by programmed cell death (apoptosis) 6-8 h after antigen exposure. antigen-induced apoptosis of immature thymocytes wa ...19921390437
antivirally protective cytotoxic t cell memory to lymphocytic choriomeningitis virus is governed by persisting antigen.the basis of antiviral protection by memory cytotoxic t lymphocytes (ctl) was investigated in vivo and in vitro using lymphocytic choriomeningitis virus (lcmv) and recombinant vaccinia viruses expressing the lcmv-glycoprotein (vacc-gp) or -nucleoprotein (vacc-np). the widely replicating lcmv with a tendency to persist induced solid long-term protective memory. the poorly replicating vaccinia recombinant viruses revealed in the vaccinated host that the antiviral capacity of the secondary immune t ...19921402673
prevalence of serum antibodies against lymphocytic choriomeningitis virus in selected populations from two u.s. cities.an elisa was developed for measuring serum antibodies against the arenavirus lymphocytic choriomeningitis virus (lcmv) and a closely related isolate termed callitrichid hepatitis virus (chv). the elisa was used to test sera from healthy adults and from hepatitis patients. in birmingham, alabama, the seropositivity rate for healthy black women was 5.1% (7/138), and the rate for patients with all types of hepatitis or cirrhosis was 4.3% (2/46). in san antonio, texas, the seropositivity rate among ...19921402829
the interplay between target organ concentrations of lymphocytic choriomeningitis virus and cell mediated immunity in baby mice.circumstantial evidence has been presented which supports the view that the fatal lcm virus infection is due to an immunological conflict in the host animal. hitherto, this outcome of the infection has only been observed in intracerebrally infected mice. in the present study, the intraperitoneal infection in young mice was investigated and the results revealed a new example of this immunological conflict. in mice infected a few days after birth, concentrations of the virus in the brain are high, ...19761266623
lcmv-specific, class ii-restricted cytotoxic t cells in beta 2-microglobulin-deficient mice.intracranial infection of normal mice with lymphocytic choriomeningitis virus (lcmv) causes meningitis and death mediated by cd8+ major histocompatibility complex (mhc) class i-restricted cytotoxic t lymphocytes (ctls). beta 2-microglobulin-deficient mice (beta 2m-/-) do not express functional mhc class i proteins and do not produce significant numbers of cd8+ t cells. when beta 2m-/- mice were infected with lcmv, many died from lcmv disease and produced a specific response to lcmv mediated by c ...19921347959
the course of lcmv infection in euthymic and athymic mice pretreated with immunomodulatory agents.balb/c (euthymic) and nu/nu (athymic) mice were treated intraperitoneally with tp-4 (a synthetic tetrapeptide, thymopoietin sequence analog) or with mannozym (1% zymosan suspension), and were infected intracerebrally with lcm virus. both of the agents contributed to the development of fatal choriomeningitis, consequently stimulated the cellular immune response in euthymic mice, but the athymic mice either treated or not, survived the infection, consequently the agents had no effect on the course ...19921343936
how can we stimulate the immune system in vivo? 19921426669
selective disruption of growth hormone transcription machinery by viral infection.viruses that establish persistent infections may show selective and unique effects on the host's transcriptional machinery. lymphocytic choriomeningitis virus (lcmv), a noncytolytic virus, can persistently infect a rat pituitary cell line. although the infected cells remain free of structural damage, virus markedly interferes with growth hormone (gh) but only minimally interferes with prolactin transcription. the study of gh promoter-chloramphenicol acetyltransferase-transfected cells and gh pro ...19921409723
cd11b (mac-1): a marker for cd8+ cytotoxic t cell activation and memory in virus infection.we have found that cd11b, a cell surface integrin of macrophages, granulocytes, and nk cells, is expressed by a subset of cd8+ t cells that include both the active virus-specific ctl and the virus-specific memory ctl populations. cd8+cd11b+ cells comprise less than 3% of naive mouse splenocytes, but after lymphocytic choriomeningitis virus (lcmv) infection increase by 9- to 12-fold by the peak (day 8) of the virus-specific ctl response. depletion of day-8 splenocytes with anti-mac-1 and c' or en ...19921500720
virus-induced acquired immune suppression by cytotoxic t cell-mediated immunopathology.acute infection with lymphocytic choriomeningitis virus causes a severe immune suppression in immunocompetent mice by triggering a t cell-mediated immunopathology, probably directed against infected macrophages and dendritic cells. an important role of gamma interferon may be to protect lymphohaemopoietic cells from virus infection and destruction by cytopathic effects of either the virus or of anti-viral immunity.19921481353
[effect of pretreatment with immunomodulating agents on the outcome of lymphocytic choriomeningitis virus infection in athymic (nude) and euthymic mice].balb/c (euthymic) and nu/nu (athymic) mice were treated intraperitoneally with tp-4 (a synthetic tetrapeptide, thymopoietin sequence analog, pharmaceutical product's factory gedeon richter, budapest, hungary) or with mannozym (0.1% zymosan suspension, institute for serobacterological production and research, human, budapest, hungary), and were infected intracerebrally with lcm virus. both of the agents contributed to the development of fatal choriomeningitis, consequently they stimulated the cel ...19921442095
vaccination or tolerance to prevent diabetes.experiments with transgenic mice expressing the glycoprotein (gp) of lymphocytic choriomeningitis virus (lcmv) under the control of the rat insulin promoter (rip) have demonstrated that potentially self-reactive t cells that normally ignore self peptides may nevertheless be induced by self peptides or "cross-reactive" foreign (e.g. viral) peptides that arise in the host in an immunogenic form; once activated these potentially self-reactive t cells may cause autoaggressive diseases (e.g. diabetes ...19921446706
roles of alpha beta and gamma delta t cell subsets in viral immunity.the current status of t-cell subset involvement in viral immunity is summarized for experimental studies in mice. the immunobiology of the normal host response is discussed, with particular reference to lymphocytic choriomeningitis (lcm) and influenza. the general impression is that cd8+ cytotoxic t lymphocytes, cd4+ th1 cells, gamma interferon, and il-2 are of major importance, with these different components of the immune system interacting to promote an optimal response. however, experiments ...19921534240
suppression of virus-specific antibody production by cd8+ class i-restricted antiviral cytotoxic t cells in vivo.the question of whether virus-induced immunosuppression includes the antibody response against the infecting virus itself was evaluated in a model situation. transgenic mice expressing the t-cell receptor (tcr) specific for peptide 32-42 of lymphocytic choriomeningitis virus (lcmv) glycoprotein 1 presented by db reacted with a strong transgenic cytotoxic t-lymphocyte (ctl) response starting on day 3 after infection with a high dose (10(6) pfu intravenously [i.v.]) of the we strain of lcmv (lcmv- ...19921583725
immunosuppression by lymphocytic choriomeningitis virus infection: competent effector t and b cells but impaired antigen presentation.lymphocytic choriomeningitis virus (lcmv) may cause a severe immunosuppression in mice. its pathogenesis is apparently dependent on lcmv-specific cd8 effector t cells that mediate the destruction of virus-infected cells which are normally essentially involved in immune responses. evaluation of various lcmv isolates in this study established a general correlation between their tropism for lymphohemopoietic cells and immunosuppression. when immune responses were assessed as the capacity of mice to ...19921623925
biochemical and immunological evidence that the 11 kda zinc-binding protein of lymphocytic choriomeningitis virus is a structural component of the virus.the completed sequence of the arenavirus, lymphocytic choriomeningitis virus, revealed a new gene encoding a small protein with a single zinc-binding domain. the cdna for this gene has been expressed in e. coli to produce fusion protein that has been used to raise antisera. the antisera facilitated the positive identification of the p11 'z' gene product as a structural component of the virion. a related arenavirus, tacaribe, has a comparable p11 gene product. the abundance of the p11 z protein r ...19921626415
clonal deletion induced by either radioresistant thymic host cells or lymphohemopoietic donor cells at different stages of class i-restricted t cell ontogeny.major histocompatibility complex (mhc) products and self-antigens expressed in the thymus determine the repertoire of mature alpha/beta t cells. while positive selection of self-mhc-restricted t cells is directed by mhc molecules expressed by thymic epithelial cells, negative selection depends to a large extent on self-antigens presented by lymphohemopoietic cells. however, radioresistant components of the thymus also influence negative selection, but it remains controversial whether this is acc ...19921533241
evidence for polyclonal b cell activation as the mechanism for lcmv-induced autoimmune hemolytic anemia.a docile substrain of lymphocytic choriomeningitis virus (lcmv) causes a persistent infection in adult c3heb mice and induces a severe autoimmune hemolytic anemia (aiha) which is maximal around three weeks post infection (pi). evaluations of serum immunoglobulin levels of these mice demonstrated grossly elevated igg2a levels along with increased igg1 and igg2b levels, suggesting that these animals also develop polyclonal b cell activation (pba). interestingly, lcmv-infected b10.br mice did not d ...19921548040
discrepancy between in vitro measurable and in vivo virus neutralizing cytotoxic t cell reactivities. low t cell receptor specificity and avidity sufficient for in vitro proliferation or cytotoxicity to peptide-coated target cells but not for in vivo protection.the tcr-alpha beta of ctl recognize peptide ag in association with mhc class i molecules. tcr binding should be highly specific to guarantee pathogen specificity and to avoid self-reactivity. therefore, the in vivo relevance of t cells exhibiting cross-reactivities in vitro and the respective role of the tcr affinities involved are not clear. to analyze high and low avidity t cell activities both in vitro and in vivo, we investigated primary and clonal ctl responses specific for the lymphocytic ...19921634779
viral infection of the thymus.we have examined infection of the thymus during congenitally acquired chronic lymphocytic choriomeningitis virus (lcmv) infection of mice, a classic model of antigen-specific t-cell tolerance. our results show that (i) infection starts at the fetal stage and is maintained throughout adulthood, and (ii) this chronic infection of the thymus can be eliminated by transfer of virus-specific cytotoxic t lymphocytes (ctl) that infiltrate the thymus and clear all viral products from both medullary and c ...19921560541
expression of tgf-beta 2 in human glioblastoma: a role in resistance to immune rejection?glioblastomas are among the most malignant tumours for which no curative treatment exists. a dysfunction of cellular immunity with decreased skin reactivity and lymphocyte blastogenesis has been described in patients with glioblastomas. in culture human glioblastoma cells release a factor termed glioblastoma-derived t cell suppressor factor (g-tsf) which inhibits the antigen-dependent growth of both helper and cytotoxic t cells. purification and cloning indicated that g-tsf is a novel member of ...19911649035
high resolution in situ hybridization to determine the cellular distribution of lymphocytic choriomeningitis virus rna in the tissues of persistently infected mice: relevance to arenavirus disease and mechanisms of viral persistence.by the application of in situ hybridization to thin sections of paraffin-embedded tissues we have been able to determine with high resolution the cell types containing lymphocytic choriomeningitis virus nucleic acid in the tissues of persistently infected mice. we confirm and extend previous observations of virus persistence in the brain, lung, liver, kidney, pancreas, thyroid and reticuloendothelial system. in addition, we demonstrate for the first time persistence of viral nucleic acid in spec ...19911649899
evidence for immune-mediated destruction as mechanism for lcmv-induced anemia in persistently infected mice.a docile substrain of lymphocytic choriomeningitis virus (lcmv) causes a persistent infection in adult c3heb mice and induces a severe anemia, which, unlike the viremia, eventually resolves. measurements of red blood cell (rbc) survival rates demonstrated an increased rate of rbc clearance in these animals, indicating a hemolytic process for the anemia. normal clearance rates of rbcs from infected mice transfused into control mice suggested that there was not an intrinsic defect in these cells. ...19911668061
effect of microbial immunomodulants on the course of lcmv infection in old mice with thymus involution.old mice with thymus involution were treated intraperitoneally with a live vaccine containing a mesogenic strain of attenuated newcastle disease virus or with mannozym (m, 1% zymosan suspension). one day after the treatments mice were infected with lymphocytic choriomeningitis virus (lcmv) intracerebrally. the fatal course of the consequent lcmv infection was stimulated by each of the pretreatments, indicating that the cellular immune response was stimulated. the results are compared with result ...19921632194
effect of mannozym on the course of lcmv infection in mice with undeveloped and normal immune system.adult germfree (gf) mice with undeveloped immune system due to antigen deficient environment, conventional (cv) mice with normal immune system and cv suckling mice with undeveloped immune system due to age were treated intraperitoneally with mannozym (m, 0.1% zymosan suspension) 4 days or 4 days and 1 day before the intracerebral inoculation with lymphocytic choriomeningitis virus (lcmv). one dose of m was equal to 40 mg/kg of zymosan. in suckling mice, both applied doses of m contributed the de ...19921632196
human-rodent contact and infection with lymphocytic choriomeningitis and seoul viruses in an inner-city population.we collected 1180 sera and 1363 questionnaires with information on demography, rodent exposure, and history of travel from persons visiting a sexually transmitted disease (std) clinic in baltimore between 1986-1988. serological tests for two rodent-borne viruses detected antibodies to lymphocytic choriomeningitis virus (lcmv) in 54 individuals (4.7%; n = 1149) and antibodies to seoul virus (seov) in three persons (0.25%; n = 1180). antibody prevalence to lcmv increased with age, but there were n ...19911672798
immune response against lymphocytic choriomeningitis virus infection in mice without cd8 expression.the immune response against lymphocytic choriomeningitis virus (lcmv) was studied in a mutant mouse strain that does not possess cd8+ t lymphocytes. virus-specific cytotoxic t cell activity was generated in spleens of wild-type mice in an acute lcmv infection but was not measurable in mutant mice. injection of replicating lcmv into footpads of wild-type mice induced a cd8+ t cell-mediated swelling that peaked on day 8, followed by a cd4+ t cell-mediated swelling that peaked on day 11, whereas mu ...19911683893
in vivo induction of cytotoxic t cell response by a free synthetic peptide requires cd4+ t cell help.most attempts to induce ctl responses by in vivo priming with free synthetic peptides have been unsuccessful so far. however, two separate studies have recently succeeded in inducing antiviral ctl responses by immunizing mice with unmodified free synthetic peptides derived from nucleoproteins from either lymphocytic choriomeningitis virus or sendai virus. in the present study, we have analyzed the cellular mechanisms by which the lymphocytic choriomeningitis virus synthetic peptide induced ctl r ...19911684372
lymphocytic choriomeningitis virus infection and house mouse (mus musculus) distribution in urban baltimore.four hundred eighty house mice (mus musculus) were trapped primarily from urban sites in baltimore, maryland from 1984 to 1989 and tested for antibody to lymphocytic choriomeningitis virus (lcmv). the majority of mice (95%) were trapped in residences at two city locations (n = 260), or in an urban park (n = 196); five additional sites were sampled. overall, 9.0% of the mice were lcmv antibody positive and infected animals were obtained from six of eight sites, including all three of the primary ...19921636880
mutations in the alpha 1 domain of a class i gene define residues important for specific allorecognition.our strategy to use saturation mutagenesis to produce an unbiased collection of major histocompatibility class i mutants has resulted in unpredicted mutant phenotypes. first, we have shown data supporting our earlier work of the dp20(y27n) mutant. allorecognition is altered at the clonal level while no variation in lymphocytic choriomeningitis virus (lcmv)-restricted recognition is observed. the defect does not destroy the integrity of this class i protein on the basis of three observations: (i) ...19901693100
mode of replication of lymphocytic choriomeningitis virus in persistently infected cultivated mouse l cells.during persistent infection of mouse l cells with strain armstrong lymphocytic choriomeningitis virus, the latter undergoes characteristic changes, including loss of mouse pathogenicity and failure to form plaques on cultivated cells. we call this virus l(arm) and have analyzed transcription and translation of its s-rna, which codes for the viral nucleoprotein (np) and the glycoprotein precursor (gp-c). in l(arm) virus-infected l cells, s-rna and genomic-sized viral complementary s-rna (vc-s-rna ...19901695411
viral escape by selection of cytotoxic t cell-resistant virus variants in vivo.viruses persist in an immune population, as in the case of influenza, or in an individual, as postulated for human immunodeficiency virus, when they are able to escape existent neutralizing antibody responses by changing their antigens. it is now shown that viruses can in principle escape the immunosurveillance of virus-specific cytotoxic t cells by mutations that alter the relevant t-cell epitope.19901696684
the role of cd4+ cells in sustaining lymphocyte proliferation during lymphocytic choriomeningitis virus infection.the murine immune response to lymphocytic choriomeningitis virus (lcmv) infection involves the activation of cd8+, class i mhc-restricted and virus-specific ctl. at times coinciding with ctl activation, high levels of il-2 gene expression and production occur, the il-2r is expressed, and t cell blastogenesis and proliferation are induced. we have previously found that, although both cd4+ and cd8+ t cell subsets transcribe il-2, the cd4+ subset appears to be the major producer of il-2 whereas the ...19911672337
restricted v-segment usage in t-cell receptors from cytotoxic t lymphocytes specific for a major epitope of lymphocytic choriomeningitis virus.cytotoxic t lymphocytes (ctl) play an important role in recovery from a number of viral infections. they are also implicated in virus-induced immunopathology as best demonstrated in lymphocytic choriomeningitis virus (lcmv) infection of adult immunocompetent mice. in the present study, the structure of the t-cell receptor (tcr) in lcmv-specific ctl in c57bl/6 (b6) mice was investigated. spleen t cells obtained from lcmv-infected mice were cultured in vitro with virus-infected stimulator cells an ...19901700830
breakdown of blood-brain barrier function in the murine lymphocytic choriomeningitis virus infection mediated by virus-specific cd8+ t cells.intracerebral inoculation of lymphocytic choriomeningitis virus (lcmv) generally results in a fatal t cell-mediated meningitis. in a previous study we have demonstrated a compromised blood-brain barrier (bbb) under such conditions. using semi-quantitative radiography and the low molecular tracer 2-amino-[1-14c]isobutyric acid we now demonstrate an uncompromised bbb in i.c. infected t cell-deficient nu/nu mice, but serious dysfunction in heterozygous littermates. transfer experiments were used to ...19911704015
antiviral antibodies attenuate t-cell-mediated immunopathology following acute lymphocytic choriomeningitis virus infection.the role of antiviral antibody in resistance to acute lymphocytic choriomeningitis virus infection has been examined by passive transfer of monoclonal antibodies and intracerebral challenge infection. protection of mice from lethal t-cell-mediated acute disease was observed following passive administration of antibodies either 1 day before or up to 2 days after infection. viral replication was suppressed in protected mice, and the cytotoxic t-cell response to virus was also diminished. virus was ...19911709692
major histocompatibility complex binding and t cell recognition of a viral nonapeptide containing a minimal tetrapeptide.the primary immune response of cytotoxic t lymphocytes in h-2d and h-2q mice to infection with lymphocytic choriomeningitis virus is directed mostly towards the common major t cell epitope of amino acids 112-132 on the viral nucleoprotein (np). the molecules responsible for presentation of the t cell epitope np112-132 are in both haplotypes the mhc class i l antigens (ld, lq). truncations of the amino and carboxy termini of the np 112-132 sequence revealed the nonapeptide rpqasgvym (np118-126) a ...19911709866
lower receptor avidity required for thymic clonal deletion than for effector t-cell function.clonal deletion in the thymus plays a major part in t-cell tolerance to self antigens. but the mechanism of negative selection, its fine specificity and the threshold of affinity and avidity remains unknown. we have now examined these aspects of negative selection with mice expressing a transgenic t-cell receptor with specificity for lymphocytic choriomeningitis virus (lcmv) glycoprotein in association with the class i h-2db molecule. these mice were rendered tolerant to lcmv by neonatal infecti ...19911710780
isolation of an arenavirus from a marmoset with callitrichid hepatitis and its serologic association with disease.callitrichid hepatitis (ch) is an acute, often fatal viral infection of new world primates from the family callitrichidae. the etiologic agent of ch is unknown. we report here the isolation of an arenavirus from a common marmoset (callithrix jacchus) with ch by using in vitro cultures of marmoset hepatocytes and vero-e6 cells. enveloped virions 67 to 133 nm in diameter with ribosomelike internal structures were seen in infected cultures. immunofluorescence and western immunoblot analysis using c ...19911712856
antiviral cytotoxic t cell response induced by in vivo priming with a free synthetic peptide.induction in vivo of antiviral cytotoxic t cell response was achieved in a mhc class i-dependent fashion by immunizing mice three times with a free unmodified 15-mer peptide derived from the nucleoprotein of lymphocytic choriomeningitis virus in ifa. the effector t cells are cd8+, restricted to the class i ld allele of the analyzed mouse strain, and are specific both at the level of secondary restimulation in vitro and at the effector t cell level. these results suggest that cocktails of viral p ...19901692084
patterns of transient expression of the arenavirus nucleocapsid protein gene in transfected cells.the cloned genes for the nucleocapsid proteins n of junín and lcm (lymphocytic choriomeningitis) arenaviruses were inserted into the sv40-derived expression vector designated pkg4. when bhk-21 (baby hamster kidney fibroblasts) and cv-1 (african green monkey kidney fibroblasts) cell lines were transfected using these constructions, the transient expression yielded a polypeptide that could not be distinguished either by size nor by immunoreactivity from the n protein synthesized during the viral i ...19911668773
involvement of both t cell receptor v alpha and v beta variable region domains and alpha chain junctional region in viral antigen recognition.we have studied the lymphocytic choriomeningitis virus (lcmv)-specific cytotoxic t cell response in transgenic mice expressing either the t cell receptor (tcr) alpha (v alpha 2/j alpha ta31) or the corresponding tcr beta (v beta 8.1/d beta/j beta 2.4) chain originally isolated from the lcmv glycoprotein specific (residues 32-42), h-2db-restricted t cell clone p14. the expression of single transgenic tcr chains did not influence the corresponding endogenous tcr v gene usage in unstimulated t cell ...19911716213
[general immunologic fundamentals and an example of virally induced immunosuppression].cell mediated and humoral immune protection against virus infections are discussed in relation to development and use of recombinant vaccines in the murine lymphocytic choriomeningitis virus infection. in the same model, immunopathological aspects of t cell immunity to viruses are examined in the murine lymphocytic choriomeningitis virus infection. this virus causes an acquired immunosuppression that is not caused by the virus itself but by cytotoxic antiviral t cd8+ effector t cells which destr ...19911724808
[virus induced acquired immunodeficiency: correlation with t cell mediated destruction of spleen and lymph node architecture].mice infected with the non-cytopathic lymphocytic choriomeningitis virus (lcmv) develop a severe acquired immune suppression. this is caused by the elimination of virus infected antigen presenting cells by cytotoxic t cells leading to a severe destruction of the follicular organization of lymphoid organs. the impairment of immune functions may allow the virus to establish persistent infections in initially immunocompetent hosts.19911724834
vaccination and protection from a lethal viral infection: identification, incorporation, and use of a cytotoxic t lymphocyte glycoprotein epitope.the outcome of infection by lymphocytic choriomeningitis virus (lcmv) is determined largely by the cytotoxic t lymphocyte (ctl) response of the host. in h-2b mice, the anti-glycoprotein (gp) response is directed to at least two epitopes, one located at gp aa 272-286 and a second in gp-1. here we show that the second epitope can be minimally identified by amino acid residues gp 34-40 (avynfat). the epitope is restricted by the db class i glycoprotein. characterization of these ctl epitopes allowe ...19901699348
ribozymes which cleave arenavirus rnas: identification of susceptible target sites and inhibition by target site secondary structure.the development of safe and effective antiviral agents has been a slow process, largely because of the difficulty in distinguishing between virus and host functions; materials toxic to the virus are frequently harmful also to the host in which the agent resides. recently, techniques which target nucleic acid sequences as a means of reducing gene expression have emerged. this antisense armamentarium includes ribozymes, rna enzymes which cleave other rna molecules in a sequence-specific manner. we ...19921738195
lymphocytic choriomeningitis outbreak associated with nude mice in a research institute.after an employee at a cancer research institute was diagnosed with lymphocytic choriomeningitis, an investigation was performed to determine the extent of lymphocytic choriomeningitis virus (lcmv) infections among the institute's employees and to identify risk factors for infection.19921740856
activated t lymphocytes from mice infected by lymphocytic choriomeningitis virus display high affinity il-2 receptors but do not proliferate in response to il-2.the i.v. injection of mice with lymphocytic choriomeningitis virus (lcmv) initiates a rapid and long lasting immunodepression which can be monitored in vivo or in vitro. splenic t lymphocytes taken from mice infected for 7 days with lcmv are characterized by a low proliferative capacity in response to con a stimulation in vitro. in an initial attempt to understand the molecular mechanisms regulating the general anergy induced by the viral infection, we have analyzed the transcription of il-2 and ...19911753103
[effect of microbial immunomodulators on the course of lymphocytic choriomeningitis virus infection in old mice with physiological thymus involution].aged mice with physiological thymus involution were treated intraperitoneally with 0.2 ml of live newcastle disease virus (ndv) containing attenuated ndv vaccine (ha titre: log 2(16)/ml) one day before or with mannozym (0.1% zymosan suspension) four days and one day before intracerebral inoculation with 100 ld50 dose of lcmv. one dose of m was equal to 40 mg/kg zymosan. both, ndv vaccine and m pretreatments contributed to the development of fatal lymphocytic choriomeningitis, thus enhanced the c ...19911785354
the expression of major histocompatibility complex (mhc) class i antigens in the brain differs markedly in acute and persistent infections with lymphocytic choriomeningitis virus (lcmv).intracranial inoculation of immunocompetent mice with lymphocytic choriomeningitis virus (lcmv) induces a fatal neurologic illness. in this disease a marked increase in mhc class i expression was found, closely associated with viral antigens and inflammatory infiltrates, in meninges, choroid plexus and ventricular ependyma but not within the brain parenchyma. immunosuppression prevented mhc induction. mice inoculated at birth had persistent infections, with lcmv antigens found primarily in neuro ...19921732281
virus zoonoses and their potential for contamination of cell cultures.silent virus infections of laboratory animals present a human health hazard, from direct exposure and from contamination of biological products for human use. here we report two recent examples. in 1989, an outbreak of lymphocytic choriomeningitis virus (lcmv) infections was recognized among workers at a cancer research center after an animal caretaker developed viral meningitis. investigation revealed that multiple tumor cell lines at the facility were infected with lcmv, as were research anima ...19911794619
operator-induced contamination in cell culture systems.operator-induced biological contamination in cell cultures is a multifaceted problem involving the unexpected introduction of other animal cells, microbial and viral contaminants. detailed studies on animal cell cross contaminations have been performed and published. the frequency of detection of problem cultures has been as high as 36% for one service performed in the usa, with interspecific cross contamination accounting for 25% and human intraspecific contamination representing 11%. awareness ...19911794620
hiv. games that viruses play. 19911721106
vaccination for disease.recombinant virus vaccines that express a limited number of epitopes are currently being developed to prevent disease by changing the relative balance between viral spread and the immune response. some circumstances, however, were found in infections with a noncytopathic virus in which vaccination caused disease; sensitive parameters included the genetic background of the host, the time or dose of infection, and the constituents of the vaccine. thus, immunopathologic damage by t cells may be an ...19911824801
seroepidemiological survey of lymphocytic choriomeningitis virus in wild house mouse (mus musculus) in yokohama port, japan.from 1985 to 1989, a total of 129 mice was captured from 7 piers of yokohama port. of these, 9 (7.0%) were positive to lymphocytic choriomeningitis virus (lcmv) antigen in indirect fluorescence antibody test. six out of 31 mice (19.4%) in 1985 and 3 out of 23 mice (13.0%) captured in 1986 were positive. all the mice (74) captured in 1988 and 1989 were negative. although 7 out of 17 mice (41.2%) in osanbashi-shinko pier and 2 out of 23 (8.7%) in honmoku pier were positive in 1985 and 1986, all mi ...19911830792
isolation of lymphocytic choriomeningitis virus from wild house mice (mus musculus) in osaka port, japan.lymphocytic choriomeningitis virus (lcmv) was isolated from 14 out of 35 wild house mouse samples captured on two piers of osaka port in japan. four of them were isolated from were isolated from 18 antibody positive mice while 10 were from 17 antibody negative mice. this is the first report of the isolation of lcmv from wild mice in japan.19911836377
molecular basis of viral persistence: a single amino acid change in the glycoprotein of lymphocytic choriomeningitis virus is associated with suppression of the antiviral cytotoxic t-lymphocyte response and establishment of persistence.isolates of lymphocytic choriomeningitis virus (lcmv) that elicit a cytotoxic t-lymphocyte response (ctl+) have been compared with isolates that suppress the ctl response (ctl-) in an effort to map this phenotype. a single amino acid change in the glycoprotein of the lcmv armstrong (arm) strain is consistently associated with the ctl- trait and the ability of the virus to persist (p+). the ctl+ p- parental strain spontaneously gives rise to ctl- p+ variants within lymphoid tissues of mice persis ...19911840619
natural killer (nk) cell response to virus infections in mice with severe combined immunodeficiency. the stimulation of nk cells and the nk cell-dependent control of virus infections occur independently of t and b cell function.the activation, proliferation, and antiviral properties of natural killer (nk) cells were examined in severe combined immunodeficiency (scid) mice to determine the influence of mature t or b cells on virus-induced nk cell functions and to more conclusively determine the antiviral properties of prototypical cd3- nk cells. nk cells were activated to high levels of cytotoxicity 3 d after infection of mice with lymphocytic choriomeningitis virus (lcmv) or murine cytomegalovirus (mcmv). analyses of s ...19911850779
in vitro selection of lymphocytic choriomeningitis virus escape mutants by cytotoxic t lymphocytes.cytotoxic t lymphocyte (ctl)-mediated cytolysis is induced via the interaction of the specific t-cell antigen receptor and the peptidic viral antigen associated with the major histocompatibility complex class i antigen. here we demonstrate in vitro that lymphocytic choriomeningitis virus (lcmv) can escape the cytotoxic activity of lcmv-specific cloned ctls by single amino acid changes within the recognized t-cell epitope defined by residues 275-289 of the lcmv glycoprotein [lcmv-gp-(275-289)]. l ...19911722316
lymphokine-activated killer cells are rejected in vivo by activated natural killer cells.a 4-h in vivo cytotoxicity assay was used to study the fate of implanted il-2-generated, lymphokine-activated killer (lak) cells in mice undergoing an activated nk cell response. 125iododeoxyuridine-labeled lak cells were rejected from selected organs of c57bl/6 mice infected with lymphocytic choriomeningitis virus or treated with il-2 or the ifn inducer poly i:c. this rejection was abrogated by the selective depletion of nk cells with antibodies to asialo-gm1 and nk1.1 ag. similar results were ...19911869833
role of viral strains and host genes in determining levels of immune complexes in a model system: implications for hiv infection.virus-antibody immune complexes form during infection with most rna and dna viruses, including those with human immunodeficiency virus (hiv). yet a subset of individuals so infected apparently does not mount such responses. to understand the principles involved, we studied the formation and deposition of virus-antibody immune complexes in the circulation in a model system utilizing mice persistently infected with lymphocytic choriomeningitis virus (lcmv). although mice of several genetic haploty ...19911812945
viral persistence in neurons explained by lack of major histocompatibility class i expression.viruses frequently persist in neurons, suggesting that these cells can evade immune surveillance. in a mouse model, 5 x 10(6) cytotoxic t lymphocytes (ctls), specific for lymphocytic choriomeningitis virus (lcmv), did not lyse infected neurons or cause immunopathologic injury. in contrast, intracerebral injection of less than 10(3) ctl caused disease and death when viral antigens were expressed on leptomeningeal and choroid plexus cells of the nervous system. the neuronal cell line obl21 express ...19911891717
protein-protein interactions in lymphocytic choriomeningitis virus.the structural organization of the lymphocytic choriomeningitis virus (lcmv) particle has been examined by triton x-114 phase separation and nearest neighbor analyses in order to define protein-protein interactions in the virion. extraction with triton x-114 established that the 44-kda membrane glycoprotein, gp-1, is a peripheral protein and that the 35-kda glycoprotein, gp-2, is an integral membrane protein. membrane permeable and membrane impermeable crosslinking reagents were used to establis ...19911853564
production of random classes of immunoglobulins in brain tissue during persistent viral infection paralleled by secretion of interleukin-6 (il-6) but not il-4, il-5, and gamma interferon.the activities of cytokines were determined in cerebrospinal fluid (csf) and serum of mice persistently or intracerebrally acutely infected with lymphocytic choriomeningitis (lcm) virus (lcmv). in contrast to cba/j (lcmv carrier) mice that responded with low levels of lcmv-specific antibody, high-responder nmri (carrier) mice showed antibody production by b cells outside of lymphoid organs. the b cells that had infiltrated the brains of lcmv carrier mice exhibited no preferential immunoglobulin ...19911899893
ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice.to address the mechanisms of tolerance to extrathymic proteins, we have generated transgenic mice expressing the lymphocytic choriomeningitis viral (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 and h-2db. these studies suggest that "peripheral tolerance" of self-reactive t cells does not involve clonal deletion, clonal anergy, or a decre ...19911901764
virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response.we investigated the potential association between viruses and insulin-dependent (type 1) diabetes (iddm) by developing a transgenic mouse model. by inserting into these mice a unique viral protein that was then expressed as a self-antigen in the pancreatic islets of langerhans, we could study the effect on that expressed antigen alone, or in concert with an induced antiviral (i.e., autoimmune) response manifested later in life in causing iddm. our results indicate that a viral gene introduced as ...19911901765
infection of lymphocytes by a virus that aborts cytotoxic t lymphocyte activity and establishes persistent infection.for viruses to establish persistent infections in their hosts, they must possess some mechanism for evading clearance by the immune system. when inoculated into adult immunocompetent mice, wild-type lymphocytic choriomeningitis virus (lcmv arm) induces a cd8(+)-mediated cytotoxic t lymphocyte (ctl) response that clears the infection within 7-14 d (ctl+ [p-]). by contrast, variant viruses isolated from lymphoid tissues of persistently infected mice fail to induce a ctl response and are thus able ...19911905339
a single amino acid substitution in an mhc class i molecule allows heteroclitic recognition by lymphocytic choriomeningitis virus-specific cytotoxic t lymphocytes.class i molecules of the mhc bind foreign and endogenous peptides allowing recognition by the tcr on ctl. the recognition and killing of cells infected with lymphocytic choriomeningitis virus (lcmv) depends on the recognition of lcmv peptides bound to class i mhc. mutations in class i mhc molecules have enabled the delineation of regions in the class i molecule important for binding peptides and for interaction with the tcr. we have constructed a library of class i mutants using saturation mutag ...19911907995
virus-triggered acquired immunodeficiency by cytotoxic t-cell-dependent destruction of antigen-presenting cells and lymph follicle structure.virus-induced acquired immune suppression in mice infected with lymphocytic choriomeningitis virus is shown here to be caused by the cd8+-t-cell-dependent elimination of macrophages/antigen-presenting cells. surprisingly, this is associated with severe destruction of the follicular organization of lymphoid organs, indicating a crucial role for dendritic cells and marginal zone macrophages in maintaining follicular structure. once established, this immunopathology cannot be readily reversed by th ...19911910175
viral persistence and disease: cytopathology in the absence of cytolysis.realising that viruses could persist and thereby cause chronic disease has been one of the major accomplishments in virology. in this review we will discuss the principles by which viruses can persist and how such persistence can lead to disease. our focus will be on the ability of certain viruses to interfere subtly with the cell's ability to produce specific differentiated products as hormones, neurotransmitters, cytokines and immunoglobulins, etc., in the absence of their ability to lyse the ...19911794088
entry of antivirally active t lymphocytes into the thymus of virus-infected mice.the thymus has long been regarded as an immunologically "privileged site" by being shielded against the entry of exogenous ag as well as protective elements of the immune system. after i.p. infection of mice, the lymphocytic choriomeningitis virus multiplied in this organ. viral ag was found predominantly in the epithelial-reticular cells of the medulla and to a lesser extent in such cells of the cortex. beginning on day 7 after infection, the virus disappeared, a process that could be blocked b ...19911898603
transcriptional analyses of baculovirus polyhedrin and foreign gene expression relative to baculovirus p10 mrna levels.comparisons have been made between the p10 and polyhedrin mrna levels recovered from spodoptera frugiperda cells infected with autographa californica nuclear polyhedrosis virus (acnpv). in molar terms and from 18 h post-infection (p.i.), the polyhedrin mrna species increased to levels one and a half times to twice as high as the p10 levels. the influence of the polyhedrin leader sequence on the expression of a foreign gene under the control of the polyhedrin promoter was investigated using a ser ...19911919531
persistent virus infections in studies of the immune response.some recent studies on immune phenomena in persistent virus infections, employing non-cytolytic viruses, are reviewed. this includes the refutation of a possible inheritance of tolerance and some aspects of drug-induced tolerance to persistent viruses, with its consequences for possible treatment of virus-induced immunopathological diseases. the biological peculiarities of viruses involved in persistent or chronic infections are discussed with respect to the balance between the immune system and ...19911930100
antibodies to lymphocytic choriomeningitis virus in wild rodent sera in egypt.specific antibodies to lymphocytic choriomeningitis (lcm) virus were detected in sera of wild rodents trapped in different regions of egypt. the highest proportion of positive sera (11.5%) was found in sinaa governorate of the asian continent, followed by sharkia governorate (5.6%) adjacent to sinaa and giza governorate (1.8%). in upper egypt, however all 610 rodent sera collected in aswan, red sea pernees and new valley adjacent to sudan were negative. the highest percentage of positive sera wa ...19911880412
a role for transforming growth factor-beta 1 in regulating natural killer cell and t lymphocyte proliferative responses during acute infection with lymphocytic choriomeningitis virus.the role of transforming growth factor beta 1 (tgf-beta 1) in regulating nk and t cell proliferation during acute viral infections was investigated. after infection of mice with lymphocytic choriomeningitis virus, nk cell proliferation peaks on day 3 and subsides by days 5 to 7 postinfection, whereas t cell proliferation peaks on day 7 and declines by days 9 to 14 postinfection. as tgf-beta 1 has been shown to inhibit lymphocyte proliferation in culture, the production and function of tgf-beta 1 ...19911918986
antiviral immune responses of fully allogeneic irradiation bone marrow mouse chimeras.in (b10.br----b10) chimeras infected with lymphocytic choriomeningitis (lcm) virus higher titers were attained in spleens and livers than in organs of the mice used for their construction, and the subsequent elimination was retarded, but eventually the virus was cleared. the numbers of lcm virus-specific ctl and their precursors as quantitated with chromium-release assay and limiting dilution method, respectively, were lower in chimeras than in b10.br or c57bl/10j mice, and fewer were restricted ...19911919008
the presence of an anti-erythrocyte autoantibody in c3heb/fej mice after lymphocytic choriomeningitis virus infection.lymphocytic choriomeningitis (lcm) virus, substrain docile, causes a chronic infection in adult c3heb/fej mice. the virus also induces a severe anemia which, unlike the viremia, eventually resolves. initially, there is frank bone marrow deficit, but the anemia persists well beyond a strong erythroid compensatory response. an immune-mediated basis for the hemolytic anemia was suggested by its abrogation in cyclophosphamide-treated mice, as well as an abnormal number of spherocytes in the circulat ...19911954312
effects of cyclosporin a on il-2 production and lymphocyte proliferation during infection of mice with lymphocytic choriomeningitis virus.the immunosuppressive agent, cyclosporin a (csa) blocks production of il-2 by lymphocytes in vitro, and impairs immune responses in vivo. during infection of mice with lymphocytic choriomeningitis virus (lcmv), il-2 is produced by spleen lymphocytes with a time course corresponding to that of t cell activation and proliferation, but distinct from nk cell activation and proliferation. to evaluate the requirement for il-2 in supporting lymphocyte proliferation in vivo, and to investigate the mecha ...19901967265
t and b cell tolerance and responses to viral antigens in transgenic mice: implications for the pathogenesis of autoimmune versus immunopathological disease.experiments with transgenic mice illustrate clonal elimination of t cells specific for antigens expressed appropriately in the thymus, but presence of inducible t cells when the antigen presented on class i mhc antigens is expressed exclusively on non-lymphohemopoietic cells in the periphery (pancreatic beta islet cells). tcr-transgenic lcmv-carrier mice expressing lcmv in the thymus exhibit clonal elimination at the early cd4+8+ thymocyte stage, causing ctl unresponsiveness in these mice. in co ...19911937540
abrogation of tolerance to a chronic viral infection.this study documents failure of peripheral tolerance mechanisms in a chronic viral infection and shows that t cell tolerance to a viral ag seen as self from fetal life can be broken despite the presence of this ag in extrathymic tissues. congenital infection of mice with lymphocytic choriomeningitis virus (lcmv) results in t cell tolerance to the virus. such mice become carriers for life harboring virus in many tissues including the thymus and exhibit no lcmv-specific ctl responses. our previous ...19911940352
quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24- or 96-well plates.titers of lymphocytic choriomeningitis virus (lcmv) were determined on adherent fibroblast cell lines in 24- or 96-well plates. after absorption of virus by cells and 48 h incubation under a methylcellulose overlay, cell monolayers were fixed with 4% formaldehyde in phosphate-buffered saline, permeabilized by incubation in 0.5% triton x-100 in balanced salt solution and then stained with a monoclonal rat anti-lcmv and a peroxidase-labeled second stage antibody. the sensitivity of the assay is wi ...19911939506
distinct sequence of negative or positive selection implied by thymocyte t-cell receptor densities.recent evidence suggests that positive and negative selection of thymocytes bearing alpha beta t-cell receptors occurs during the predominant double-positive (cd4+cd8+) stage. but the sequence or stage at which positive or negative selection occurs during thymocyte maturation has not been well defined. here we use transgenic mice to show that the cd4+cd8+ stage might be further subdivided into cd3lo (low) and cd3in (intermediate) stages. the cd3in stage could represent t cells that have been pos ...19901975427
molecular insights into infections of the central nervous system. 19901970189
virus-specific delayed-type hypersensitivity (dth). cells mediating lymphocytic choriomeningitis virus-specific dth reaction in mice.we had previously shown that the local lymphocytic choriomeningitis virus-induced delayed-type hypersensitivity (dth) reaction in mice consists of two well delineated phases that are mediated by cd8+ and cd4+ t lymphocytes, respectively. these findings have been confirmed and extended by showing that the first cd8+ cell-dependent part of the response was enhanced by either the presence of cd4+ cells or systemic treatment with il-2 and that it developed in the absence of detectable numbers of mon ...19901968492
viruses as therapeutic agents. i. treatment of nonobese insulin-dependent diabetes mice with virus prevents insulin-dependent diabetes mellitus while maintaining general immune competence.a situation in which virus can be used as a therapeutic agent to prevent a lethal autoimmune disease is explored. nonobese insulin-dependent diabetes (nod) mice spontaneously develop insulin-dependent diabetes mellitus (iddm), characterized by lymphocytic infiltration into the islets of langerhans and beta cell destruction, resulting in hypoinsulinemia, hyperglycemia, ketoacidosis, and death. infection of nod mice with lymphocytic choriomeningitis virus (lcmv) aborts the autoimmune manifestation ...19901972180
persistent infection with lymphocytic choriomeningitis virus enhances expression of mhc class i glycoprotein on cultured mouse brain endothelial cells.brain endothelial cells (ec) represent a major component of the blood/brain barrier, which activated ctl cross to enter the central nervous system. several viruses also penetrate the central nervous system through the blood stream via the brain ec. the studies reported here focus on understanding the principles and consequences of interactions among viruses, lymphocytes, and ec in the brain. as shown persistent but not acute infection by lymphocytic choriomeningitis virus enhances the expression ...19912033264
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