Publications

humoral immunity due to long-lived plasma cells.	conventional models suggest that long-term antibody responses are maintained by the continuous differentiation of memory b cells into antibody-secreting plasma cells. this is based on the notion that plasma cells are short-lived and need to be continually replenished by memory b cells. we examined the issue of plasma cell longevity by following the persistence of lcmv-specific antibody and plasma cell numbers after in vivo depletion of memory b cells and by adoptive transfer of virus-specific pl ...	1998	9529153
sequence and characterisation of the z gene encoding ring finger protein of the lymphocytic choriomeningitis virus mx strain.	we have cloned and characterised a cdna encoding z protein of recently identified mx strain of lymphocytic choriomeningitis virus (lcmv) persistently infecting human matu cells. deduced amino acid sequence of lcmv mx z protein showed 88.9% identity with that of the lcmv armstrong (arm) strain and 80.9% identity with that of the lcmv traub (tra) strain. it contained conserved zinc-binding ring finger domain and c-terminal proline-rich region. northern blot analysis of total rna from matu cells re ...	1998	10358742
an arenavirus ring (zinc-binding) protein binds the oncoprotein promyelocyte leukemia protein (pml) and relocates pml nuclear bodies to the cytoplasm.	the promyelocytic leukemia protein (pml) forms nuclear bodies which are altered in some disease conditions. we report that the cytoplasmic rna virus lymphocytic choriomeningitis virus (lcmv) influences the distribution of pml bodies. in cells infected with lcmv, the z protein and pml form large bodies primarily in the cytoplasm. transient transfection studies indicate that z alone is sufficient to redistribute pml to the cytoplasm and that pml and z colocalize. coimmunoprecipitation studies show ...	1998	9420283
identification of db- and kb-restricted subdominant cytotoxic t-cell responses in lymphocytic choriomeningitis virus-infected mice.	antiviral cytotoxic t-cells are critical for control of lymphocytic choriomeningitis virus (lcmv) infection in mice. in h-2b mice, the antiviral response is directed against three db-restricted epitopes in the viral nucleoprotein (np396-404) and glycoprotein (gp276-286 and gp33-41). our present data revealed a clear hierarchy among these three epitopes, in which np396-404 is immunodominant, followed by gp33-41 and gp276-286, respectively. in order to identify additional ctl epitopes in the lcmv ...	1998	9448700
normal responsiveness of ctla-4-deficient anti-viral cytotoxic t cells.	ctla-4 has been proposed to negatively regulate immune responses, and mice deficient for ctla-4 expression succumb to a lymphoproliferative disorder within a few weeks after birth. this study assessed the responsiveness of ctla-4-deficient t cells expressing a class i-restricted tcr specific for lymphocytic choriomeningitis virus (lcmv). the kinetics of t cell proliferation were studied in vitro after stimulation of t cells with full and partial t cell agonists. no gross abnormalities in ctla-4- ...	1998	9551960
dendritic cells efficiently induce protective antiviral immunity.	cytotoxic t lymphocytes (ctl) are essential for effective immunity to various viral infections. because of the high speed of viral replication, control of viral infections imposes demanding functional and qualitative requirements on protective t-cell responses. dendritic cells (dc) have been shown to efficiently acquire, transport, and present antigens to naive ctl in vitro and in vivo. in this study, we assessed the potential of dc, either pulsed with the lymphocytic choriomeningitis virus (lcm ...	1998	9557664
two ring finger proteins, the oncoprotein pml and the arenavirus z protein, colocalize with the nuclear fraction of the ribosomal p proteins.	the promyelocytic leukemia (pml) protein forms nuclear bodies which are relocated to the cytoplasm by the rna virus lymphocytic choriomeningitis virus (lcmv). the viral z protein directly binds to pml and can relocate the nuclear bodies. others have observed that lcmv virions may contain ribosomes; hence, we investigated the effects of infection on the distribution of ribosomal p proteins (p0, p1, and p2) with pml as a reference point. we demonstrate an association of pml bodies with p proteins ...	1998	9557665
the numbers game for virus-specific cd8+ t cells.		1998	9565533
induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic t lymphocytes visualized using soluble tetrameric major histocompatibility complex class i-peptide complexes.	this study describes the construction of soluble major histocompatibility complexes consisting of the mouse class i molecule, h-2db, chemically biotinylated beta2 microglobulin and a peptide epitope derived from the glycoprotein (gp; amino acids 33-41) of lymphocytic choriomeningitis virus (lcmv). tetrameric class i complexes, which were produced by mixing the class i complexes with phycoerythrin-labeled neutravidin, permitted direct analysis of virus-specific cytotoxic t lymphocytes (ctls) by f ...	1998	9565631
evaluation of the galalpha1-3gal epitope as a host modification factor eliciting natural humoral immunity to enveloped viruses.	human sera contain high levels of natural antibody (ab) to galalpha1-3gal, a terminal glycosidic structure expressed on the surface of cells of mammals other than old world primates. incorporation of this determinant onto retroviral membranes by passage of viruses in cells encoding alpha-1-3-galactosyltransferase (gt) renders retroviruses sensitive to lysis by natural ab and complement in normal human serum (nhs). plasma membrane-budding viruses representing four additional virus groups were exa ...	1998	9573228
protective immunity does not correlate with the hierarchy of virus-specific cytotoxic t cell responses to naturally processed peptides.	infection of c57bl/6 mice with lymphocytic choriomeningitis virus (lcmv) stimulates major histocompatibility complex class i-restricted cytotoxic t cells (ctls), which normally resolve the infection. three peptide epitopes derived from lcmv have been shown to bind the mouse class i molecule h-2 db and to stimulate ctl responses in lcmv-infected mice. this report describes the identity and abundance of each ctl epitope after their elution from lcmv-infected cells. based on this information, pepti ...	1998	9584143
cd4+ and cd8+ t cell interactions in ifn-gamma and il-4 responses to viral infections: requirements for il-2.	cytokine responses to lymphocytic choriomeningitis virus infections were evaluated, and cd8+ t cell, cd4+ t cell, and il-2 contributions delineated. in immunocompetent mice, lymphocytic choriomeningitis virus induced both ifn-gamma and il-4 as well as il-2. experiments in mice either beta2-microglobulin-deficient, lacking mhc class i molecules and cd8+ t cells, or a beta(b)-deficient, lacking mhc class ii molecules and cd4+ t cells, demonstrated that mixtures of t cell responses were required fo ...	1998	9590250
aplastic anemia rescued by exhaustion of cytokine-secreting cd8+ t cells in persistent infection with lymphocytic choriomeningitis virus.	aplastic anemia may be associated with persistent viral infections that result from failure of the immune system to control virus. to evaluate the effects on hematopoiesis exerted by sustained viral replication in the presence of activated t cells, blood values and bone marrow (bm) function were analyzed in chronic infection with lymphocytic choriomeningitis virus (lcmv) in perforin-deficient (p0/0) mice. these mice exhibit a vigorous t cell response, but are unable to eliminate the virus. withi ...	1998	9607930
absence of tnfrp55 influences virus-induced autoimmunity despite efficient lymphocytic infiltration.	tumor necrosis factor (tnf)-alpha is a multipotent cytokine associated with many cellular functions, including inflammation and anti-viral defense. many studies have implicated tnf-alpha in the pathogenesis of autoimmune diseases. tnf-alpha responses are mediated through binding to specific cell surface receptors, tnfrp55 and tnfrp75. the objective of the present study was to investigate the contribution of the tnfrp55 in the inflammatory response associated with autoimmune diabetes development ...	1998	9620596
lcmv cdna formation: which reverse transcriptase is responsible?		1998	9635404
role of co-stimulation in cd8+ t cell activation.	the two-signal model states that activation of naive t cells requires a signal 1 stimulus through the tcr and a co-stimulatory signal 2. by contrast, signal 1 alone is sufficient for pre-activated t cells. recently, however, it has been shown that under certain conditions t cells can bypass the requirement for co-stimulation. for example, cd28-deficient mice, when immunized with lymphocytic choriomeningitis virus, mount a vigorous cytotoxic t lymphocyte response and clear the virus. as a continu ...	1998	9645610
stability of virus-specific cd4+ t cell frequencies from acute infection into long term memory.	mice infected with viruses develop long-lasting high frequency memory cd8+ t cell pools, but much less is known about the cd4+ t cell response. facs analysis revealed the modulation of several activation markers on cd4+ t cells during an acute infection with lymphocytic choriomeningitis virus (lcmv), consistent with an activated cell phenotype. examination of virus-specific cytokine production using elispot assays showed a significant increase in the number of ifn-gamma-secreting cells in the sp ...	1998	9647245
modelling the dynamics of lcmv infection in mice: conventional and exhaustive ctl responses.	lymphocytic choriomeningitis virus (lcmv) infection in mice provides an example of an extraordinarily dynamic process with an extreme sensitivity of phenotype of infection to parameters of virus/host interaction. a mathematical model is developed to examine the dynamics of virus-specific cytotoxic t lymphocyte (ctl) response for lcmv infection in mice. the model, formulated by a system of nonlinear delay-differential equations, considers the interacting populations of viruses, precursor ctls, te ...	1998	9650288
a rash, circulating anticoagulant, then meningitis.		1998	9652671
conserved t cell receptor repertoire in primary and memory cd8 t cell responses to an acute viral infection.	viral infections often induce potent cd8 t cell responses that play a key role in antiviral immunity. after viral clearance, the vast majority of the expanded cd8 t cells undergo apoptosis, leaving behind a stable number of memory cells. the relationship between the cd8 t cells that clear the acute viral infection and the long-lived cd8 memory pool remaining in the individual is not fully understood. to address this issue, we examined the t cell receptor (tcr) repertoire of virus-specific cd8 t ...	1998	9653085
antiviral protection and germinal center formation, but impaired b cell memory in the absence of cd19.	coligation of cd19, a molecule expressed during all stages of b cell development except plasmacytes, lowers the threshold for b cell activation with anti-igm by a factor of 100. the cytoplasmic tail of cd19 contains nine tyrosine residues as possible phosphorylation sites and is postulated to function as the signal transducing element for complement receptor (cr)2. generation and analysis of cd19 gene-targeted mice revealed that t cell-dependent (td) antibody responses to proteinaceous antigens ...	1998	9653091
role of interferon-gamma in the pathogenesis of lcmv-induced meningitis: unimpaired leucocyte recruitment, but deficient macrophage activation in interferon-gamma knock-out mice.	generally, interferon-gamma (ifn-gamma) is considered a critical regulator of t cell mediated inflammation. for this reason, we investigated the pathogenesis of lymphocytic choriomeningitis in mice with a targeted defect of the gene encoding this cytokine. our results revealed that ifn-gamma is redundant in the afferent phase of the antiviral t cell response as well as a local mediator of this t cell mediated inflammatory disease. however, ifn-gamma may play an indirect role as it is involved in ...	1998	9663567
alterations in cell surface carbohydrates on t cells from virally infected mice can distinguish effector/memory cd8+ t cells from naive cells.	glycosylation changes on surface molecules of t cells affect cell trafficking and function and may be useful in discriminating between naive, effector, and memory t cells. to analyze oligosaccharide structures on t cells activated in vivo, we examined alterations in sialic acid residues on t cells following infection of mice with lymphocytic choriomeningitis (lcmv), vaccinia virus, and vesicular stomatitis virus. we found that the majority of cd8 t cells from mice acutely infected with these vir ...	1998	9670938
delivery of epitopes by the salmonella type iii secretion system for vaccine development.	avirulent strains of salmonella typhimurium are being considered as antigen delivery vectors. during its intracellular stage in the host, s. typhimurium resides within a membrane-bound compartment and is not an efficient inducer of class i-restricted immune responses. viral epitopes were successfully delivered to the host-cell cytosol by using the type iii protein secretion system of s. typhimurium. this resulted in class i-restricted immune responses that protected vaccinated animals against le ...	1998	9677200
cd40 ligand-mediated interactions are involved in the generation of memory cd8(+) cytotoxic t lymphocytes (ctl) but are not required for the maintenance of ctl memory following virus infection.	cd8(+) cytotoxic t lymphocytes (ctl) play a key role in the control of many virus infections, and the need for vaccines to elicit strong cd8(+) t-cell responses in order to provide optimal protection in such infections is increasingly apparent. however, the mechanisms involved in the induction and maintenance of cd8(+) ctl memory are currently poorly understood. in this study, we investigated the involvement of cd40 ligand (cd40l)-mediated interactions in these processes by analyzing the memory ...	1998	9696840
the original sin of killer t cells.		1998	9697760
original antigenic sin impairs cytotoxic t lymphocyte responses to viruses bearing variant epitopes.	some viruses, including human immunodeficiency virus (hiv) and hepatitis b virus (hbv) in humans, and lymphocytic choriomeningitis virus (lcmv) in mice, are initially controlled by cytotoxic t lymphocytes (ctls), but may subsequently escape through mutation of the relevant t-cell epitope. some of these mutations preserve the normal binding to major histocompatibility complex class i molecules, but present an altered surface to the t-cell antigen receptor. the exact role of these so-called altere ...	1998	9697771
positive selection of low responsive, potentially autoreactive t cells induced by high avidity, non-deleting interactions.	using a novel cell suspension model we investigated the relative abilities of nominal peptide and variants thereof to modulate de novo positive selection of lymphocytic choriomeningitis virus (lcmv)-specific tcr transgenic t cells. confirming our earlier findings intermediate concentrations (10(-7) to 10(-5) m) of the nominal agonist peptide, p33, induced cd8 co-receptor down-modulation at the level of the entire receptor and the cd8beta chain as a consequence of high but non-deleting signal int ...	1998	9701038
formation of tcr dimers/trimers as a crucial step for t cell activation.	t cell activation involves specific interactions between the tcr and peptides presented by the mhc. this engagement leads to phosphorylation and subsequent internalization of the tcr complex. by analyzing the kinetics of the internalization of tcr, we found that the rate of tcr down-regulation was proportional to the square of the tcr density. mathematical modeling of tcr interactions indicates that such a relation is only possible if tcr dimerize before internalization. by mathematical analysis ...	1998	9710234
lymphocytic choriomeningitis virus-induced alterations of t helper-mediated responses in mice developing autoimmune hemolytic anemia during the course of infection.	the effect of lcmv on cd4+ t lymphocytes was analyzed in c3heb/fej mice after infection with the docile strain of this virus. our results indicated that lcmv triggers: i) an inhibition of th2 lymphocyte differentiation induced by concomitant immunization with a nonviral protein antigen; ii) a depression of t helper-dependent antibody responses elicited by such an immunization; and iii) a cd4+ cell-mediated proliferation of spleen cells leading to increased interleukin-4 and interferon-gamma mess ...	1998	9714079
tumor-infiltrating lymphocytes exhibiting high ex vivo cytolytic activity fail to prevent murine melanoma tumor growth in vivo.	the identification of tumor-associated ags recognized by cd8+ ctl and prevention of tumor outgrowth by adoptive transfer of these ctl demonstrates that cd8+ t cells play a major role in antitumor immunity. we have generated b16.f10 melanoma cells that express the glycoprotein epitope amino acid 33-41 (gp33) of the lymphocytic choriomeningitis virus (lcmv) to examine antitumor cd8+ t cell response in c57bl/6 mice immune to lcmv and in mice transgenic for the lcmv gp33-specific p14 tcr (p14 tcr mi ...	1998	9725210
incomplete trifluoroacetic acid deprotection of asparagine-trityl-protecting group in the vicinity of a reduced peptide bond.	during the fmoc solid-phase synthesis of reduced peptide bond analogues, we observed that the trityl protection of an asparagine residue in the vicinity of a reduced peptide bond is not cleaved completely after the final trifluoroacetic acid deprotection step. the relative position of the asn side-chain amine and of the aminomethylene bond as well as the preferential protonation of the secondary amine can be used to explain this phenomenon. we show that longer deprotection times or the use of me ...	1998	9727866
antigen expressed on tumor cells fails to elicit an immune response, even in the presence of increased numbers of tumor-specific cytotoxic t lymphocyte precursors.	we have used t-cell receptor (tcr) transgenic mice to analyze the interaction of tumors with the immune system. we show that the tumor cell line lewis lung-lymphocytic choriomeningitis virus (ll-lcmv), genetically manipulated to express an h-2 db-restricted epitope of the lymphocytic choriomeningitis virus glycoprotein (lcmv33-41), can grow progressively in tcr transgenic mice, where approximately 50% of cd8+ t cells are specific for lcmv33-41. tcr transgenic t cells were not deleted in tumor-be ...	1998	9731502
apoptotic regulation of t cells and absence of immune deficiency in virus-infected gamma interferon receptor knockout mice.	acute viral infections often induce a transient period of immune deficiency in which the host's t cells fail to proliferate in response to t-cell mitogens and fail to make an antigen-specific memory recall response. this has been associated with the enhanced sensitivity of these highly activated t cells to undergo apoptosis, or activation-induced cell death (aicd), upon t-cell receptor ligation. here we show that gamma interferon receptor-deficient (ifn-gamma r-/-) mice mount a t-cell response t ...	1998	9733817
long-term cd4 th1 and th2 memory following acute lymphocytic choriomeningitis virus infection.	cd4 t cells play a central role in viral immunity. they provide help for b cells and cd8 t cells and can act as effectors themselves. despite their importance, relatively little is known about the magnitude and duration of virus-specific cd4 t-cell responses. in particular, it is not known whether both cd4 th1 memory and cd4 th2 memory can be induced by viral infections. to address these issues, we quantitated virus-specific cd4 th1 (interleukin 2 [il-2] and gamma-interferon) and th2 (il-4) resp ...	1998	9733872
the art of tolerance.		1998	9734388
antigen persistence and time of t-cell tolerization determine the efficacy of tolerization protocols for prevention of skin graft rejection.	we studied antigen-specific t-cell tolerization therapy using skin transplantation across a defined minor histocompatibility antigen difference. specific tolerization protocols using short-lived peptide or long-lived spleen cells presenting the peptide as antigen prevented graft rejection without immunosuppression when started before or as long as 10 days after transplantation. peptide-induced t-cell tolerance was transient, and antigen presentation by the graft was not sufficient to maintain to ...	1998	9734393
the impact of variation in the number of cd8(+) t-cell precursors on the outcome of virus infection.	we investigated the role of varying the initial number of naive antiviral ctl precursors on the dynamics of lcmv-docile infection. c57bl/6 mice, exhibiting lcmv-specific ctlp frequencies of about 50, are protected against virus persistence over a range of infectious doses up to 10(4) pfu. with 10-fold higher doses, a 100-fold increase in ctlp is required to restore virus control. with doses above 10(6) pfu, elevation of the initial ctlp number leads only to lethal immunopathology. similarly, a 1 ...	1998	9758696
detection of a high frequency of virus-specific cd4+ t cells during acute infection with lymphocytic choriomeningitis virus.	lymphocytic choriomeningitis virus (lcmv), like many viruses, induces a profound activation and expansion of cd8+ t cells. in contrast, cd4+ t cells do not increase in total number during the acute infection. we show here that mice infected with lcmv have a low but detectable frequency (<1/300) of cd4+ t cells, as detected by il-2 production in limiting dilution assays, to each of two class ii peptides during the peak of the acute lcmv response and into long-term memory. however, during the peak ...	1998	9759834
dissemination of lymphocytic choriomeningitis virus from the gastric mucosa requires g protein-coupled signaling.	the gastric mucosa is an important portal of entry for lymphocytic choriomeningitis virus (lcmv) infections. within hours after intragastric (i.g.) inoculation, virus appears in the gastric epithelia, then in the mesenteric lymph nodes and spleen, and then in the liver and brain. by 72 h i.g.-inoculated virus is widely disseminated and equivalent to intravenous (i.v.) infection (s. k. rai, b. k. micales, m. s. wu, d. s. cheung, t. d. pugh, g. e. lyons, and m. s. salvato. am. j. pathol. 151:633-6 ...	1998	9765400
evidence for an underlying cd4 helper and cd8 t-cell defect in b-cell-deficient mice: failure to clear persistent virus infection after adoptive immunotherapy with virus-specific memory cells from mumt/mumt mice.	adoptive transfer of virus-specific memory lymphocytes can be used to identify factors and mechanisms involved in the clearance of persistent virus infections. to analyze the role of b cells in clearing persistent infection with lymphocytic choriomeningitis virus (lcmv), we used b-cell-deficient mumt/mumt (b-/-) mice. b-/- mice controlled an acute lcmv infection with the same kinetics and efficiency as b-cell-competent (b+/+) mice via virus-specific, major histocompatibility complex (mhc) class ...	1998	9765468
dendritic cells induce autoimmune diabetes and maintain disease via de novo formation of local lymphoid tissue.	activation of autoreactive t cells can lead to autoimmune diseases such as insulin-dependent diabetes mellitus (iddm). the initiation and maintenance of iddm by dendritic cells (dc), the most potent professional antigen-presenting cells, were investigated in transgenic mice expressing the lymphocytic choriomeningitis virus glycoprotein (lcmv-gp) under the control of the rat insulin promoter (rip-gp mice). we show that after adoptive transfer of dc constitutively expressing the immunodominant cyt ...	1998	9782126
an inhibitor of hiv-1 protease modulates proteasome activity, antigen presentation, and t cell responses.	inhibitors of the protease of hiv-1 have been used successfully for the treatment of hiv-1-infected patients and aids disease. we tested whether these protease inhibitory drugs exerted effects in addition to their antiviral activity. here, we show in mice infected with lymphocytic choriomeningitis virus and treated with the hiv-1 protease inhibitor ritonavir a marked inhibition of antiviral cytotoxic t lymphocyte (ctl) activity and impaired major histocompatibility complex class i-restricted epi ...	1998	9789051
cd40 ligand is pivotal to efficient control of virus replication in mice infected with lymphocytic choriomeningitis virus.	cd40 ligand (cd40l) is an important molecule that is known to be involved in t-b collaboration and certain aspects of cell-mediated immunity. however, its role in antiviral immunity has not been clearly defined as of yet. therefore, mice with a targeted defect in the gene encoding this molecule were infected with one of two strains of lymphocytic choriomeningitis virus differing markedly in their capacity to spread in the host. infection with lymphocytic choriomeningitis virus is initially contr ...	1998	9794385
transgenic expression of ifn-alpha in the central nervous system of mice protects against lethal neurotropic viral infection but induces inflammation and neurodegeneration.	type i ifns, which include ifn-alpha, appear to have complex and broad-ranging actions in the central nervous system (cns) that may result in protection or injury. to better understand these issues, we generated transgenic mice that produce ifn-alpha1 chronically from astrocytes. these glial fibrillary acidic protein-ifn-alpha transgenic mice developed a progressive inflammatory encephalopathy, with marked calcium mineralization, meninoencephalitis, gliosis, and neurodegeneration. many features ...	1998	9794439
in vivo treatment with a mhc class i-restricted blocking peptide can prevent virus-induced autoimmune diabetes.	we tested the in vivo potential of a mhc class i-restricted blocking peptide to sufficiently lower an anti-viral ctl response for preventing virus-induced ctl-mediated autoimmune diabetes (insulin-dependent diabetes mellitus (iddm)) in vivo without affecting systemic viral clearance. by designing and screening several peptides with high binding affinities to mhc class i h-2db for best efficiency in blocking killing of target cells by lymphocytic choriomeningitis virus (lcmv) and other viral ctl, ...	1998	9794447
hierarchies of antigen-specific cytotoxic t-cell responses.	studies carried out using either mice or humans have shown that cytotoxic t-lymphocyte (ctl) responses to many different pathogenic organisms often comprise ctl specific for multiple class i-restricted peptide epitopes. differences in the magnitude of epitope-specific ctl responses appear to arise mainly from differences in the expression level of the corresponding class i/peptide complex on the surface of the antigen-presenting cell. the size of the ctl response may be limited by the frequency ...	1998	9795761
protective heterologous antiviral immunity and enhanced immunopathogenesis mediated by memory t cell populations.	a basic principle of immunology is that prior immunity results in complete protection against a homologous agent. in this study, we show that memory t cells specific to unrelated viruses may alter the host's primary immune response to a second virus. studies with a panel of heterologous viruses, including lymphocytic choriomeningitis (lcmv), pichinde (pv), vaccinia (vv), and murine cytomegalo (mcmv) viruses showed that prior immunity with one of these viruses in many cases enhanced clearance of ...	1998	9802982
comparison of activation versus induction of unresponsiveness of virus-specific cd4+ and cd8+ t cells upon acute versus persistent viral infection.	the functional status of cd4+ t cells during establishment of persistent infection with the noncytopathic lymphocytic choriomeningitis virus was assessed and compared to that of cytotoxic cd8+ t cells. functionality of virus-specific cd4+ t cells was measured by proliferative responses, cytokine secretion, cognate help, and ifngamma-mediated protection against challenge infection with recombinant vaccinia virus. functional cd4+ t cells were induced early after infection and remained measurable u ...	1998	9806631
transient alteration of t cell fine specificity by a strong primary stimulus correlates with t cell receptor down-regulation.	p14 mice expressing a transgenic tcr specific for the lymphocytic choriomeningitis virus glycoprotein p33 epitope were used to study the induction of ctl effector activity by a variety of ligands. surprisingly, p33 variants which are weaker agonists for the p14 tcr than the wild-type p33 peptide were able to induce more potent effectors with a broader range of cytolytic specificity. similarly, low concentrations of p33 were more effective than higher concentrations. these results correlated with ...	1998	9808168
inhibition of tcr triggering by a spectrum of altered peptide ligands suggests the mechanism for tcr antagonism.	understanding the parameters involved in t cell activation has been complicated by the discovery of partial t cell agonists. altered peptide ligands (apl) have recently shown that different subsets of t cell responses can be selectively activated by certain peptides, which define a hierarchy of t cell activation. for cytotoxic t cells, this hierarchy ranges from sensitizing target cells for lysis through proliferation to effector cell induction. the degree of tcr down-regulation mediated by apl- ...	1998	9808179
a protective cytotoxic t cell response to a subdominant epitope is influenced by the stability of the mhc class i/peptide complex and the overall spectrum of viral peptides generated within infected cells.	this study identifies instability of mhc class i/peptide complexes and intermolecular competition for mhc class i presentation as factors responsible for the subdominance of cytotoxic t lymphocyte (ctl) epitopes. this evidence is based on the characterization of a new ctl epitope derived from the glycoprotein (gp) of lymphocytic choriomeningitis virus (lcmv). this epitope, peptide gp117-125 (gp117) is presented to t cells by the mouse mhc class i molecule, h-2db. in short-term experiments induct ...	1998	9808199
an adult thymic stromal-cell suspension model for in vitro positive selection.	presented here is a cell-suspension model for positive selection using thymocytes from alphabeta-tcr (h-2db-restricted) transgenic mice specific to the lymphocytic choriomeningitis virus (lcmv) on a nonselecting mhc background (h-2d or tap-1 -/-), cocultured with freshly isolated adult thymus stromal cells of the selecting mhc type. the thymic stromal cells alone induced positive selection of functional cd4- cd8+ cells whose kinetics and efficiency were enhanced by nominal peptide. fibroblasts e ...	1998	9814589
differentiation of naive ctl to effector and memory ctl: correlation of effector function with phenotype and cell division.	phenotypically and functionally, the early steps of t cell differentiation are not well characterized. in addition, the effector t cell stage shares several phenotypic characteristics with memory t cells, which has made the analysis of t cell memory difficult. in this study, we have investigated in vitro and in vivo the differentiation of naive ctl into effector and memory ctl as a function of cell division using lymphocytic choriomeningitis virus-specific tcr-transgenic spleen cells labeled wit ...	1998	9820507
the proteasome inhibitor lactacystin prevents the generation of an endoplasmic reticulum leader-derived t cell epitope.	the presentation of viral antigens on mhc class i molecules requires their intracellular fragmentation into peptides of appropriate length and anchor residue positions. evidence has accumulated that the proteasome is the endoprotease in charge of the generation of mhc class i ligands in the cytoplasm. the generation of t cell epitopes derived from the leader peptides of endoplasmic reticulum (er) targeted proteins, however. has been reported to be independent of the proteasome. here we show that ...	1998	9823757
stability and diversity of t cell receptor repertoire usage during lymphocytic choriomeningitis virus infection of mice.	numerous studies have examined t cell receptor (tcr) usage of selected virus-specific t cell clones, yet little information is available regarding the stability and diversity of tcr repertoire usage during viral infections. here, we analyzed the vbeta8.1 tcr repertoire directly ex vivo by complementarity-determining region 3 (cdr3) length spectratyping throughout the acute lymphocytic choriomeningitis virus (lcmv) infection, into memory, and under conditions of t cell clonal exhaustion. the vbet ...	1998	9841914
identification of alpha-dystroglycan as a receptor for lymphocytic choriomeningitis virus and lassa fever virus.	a peripheral membrane protein that is interactive with lymphocytic choriomeningitis virus (lcmv) was purified from cells permissive to infection. tryptic peptides from this protein were determined to be alpha-dystroglycan (alpha-dg). several strains of lcmv and other arenaviruses, including lassa fever virus (lfv), oliveros, and mobala, bound to purified alpha-dg protein. soluble alpha-dg blocked both lcmv and lfv infection. cells bearing a null mutation of the gene encoding dg were resistant to ...	1998	9851928
b cell responses and immune memory.		1998	9855420
sequence comparison of the large genomic rna segments of two strains of lymphocytic choriomeningitis virus differing in pathogenic potential for guinea pigs.	two strains of lymphocytic choriomeningitis virus (lcmv) differ in their ability to cause a lethal disease in outbred guinea pigs: the armstrong (arm) strain is not lethal at high doses (10(6) pfu), whereas the we strain is lethal at less than 10 pfu inoculated intraperitoneally. the high pathogenic potential of lcmv we has been mapped to the larger (l) of the two genomic rna segments by genetic reassortment analysis (riviere, y., ahmed, r., southern, p. j., buchmeier, m. j. and oldstone, m. b. ...	1998	9857988
the critical need for cd4 help in maintaining effective cytotoxic t lymphocyte responses.		1998	9858506
viral immune evasion due to persistence of activated t cells without effector function.	we examined the regulation of virus-specific cd8 t cell responses during chronic lymphocytic choriomeningitis virus (lcmv) infection of mice. our study shows that within the same persistently infected host, different mechanisms can operate to silence antiviral t cell responses; cd8 t cells specific to one dominant viral epitope were deleted, whereas cd8 t cells responding to another dominant epitope persisted indefinitely. these virus-specific cd8 t cells expressed activation markers (cd69(hi), ...	1998	9858507
virus-activated cd8 t cells and lymphokine-activated nk cells express the mast cell function-associated antigen, an inhibitory c-type lectin.	the mast cell function-associated ag (mafa) is an inhibitory c-type lectin that was originally identified on the cell surface of a rat mucosal mast cell line, rbl-2h3. we have cloned the mouse homologue of the rat mafa gene, and northern blot analysis revealed that mouse mafa (mmafa) gene expression was strongly induced in effector cd8 t cells and lymphokine-activated nk cells but not in effector cd4 t cells and in mouse mast cells. moreover, mmafa gene expression was only found in effector cd8 ...	1998	9862665
[herpes simplex and lymphocytic choriomeningitis viruses in infections of the central nervous system--clinical and cerebrospinal fluid characteristics].	a great number of various viruses are stated as the cause of acute infections and damages of the central nervous system. in most cases these are minor damages which exhibit as meningeal syndrome and a specific finding in the cerebrospinal fluid. according to the dominant location, central nervous system infections can take a form of meningitis, encephalitis or myelitis. since the inflammatory process of the meninges can not be separated from the inflammatory process of the brain, we usually spea ...	1998	9863335
selective immunotherapy of iddm: a discussion based on new findings from the rip-lcmv model for autoimmune diabetes.		1998	9865317
modulation of the cellular immune response to intracerebral lymphocytic choriomeningitis virus (lcmv) infection in mice.	certain viruses do not kill the cells they infect. the immunological response of the host in such situations may be involved in the development of pathologic changes and clinical illness. pioneering work by rowe has shown that death associated with acute lcmv infection in the mouse is resulted from the immune response. many investigators using a variety of techniques including neonatal thymectomy, irradiation, or treatment of adult mice with antilymphoid drugs or antithymocyte sera have confirme ...	1998	9873940
a welcome mat for leprosy and lassa fever.		1998	9874652
dynamics of the cd8+ t cell response during acute lcmv infection.		1998	9889965
in vivo dynamics of anti-viral cd8 t cell responses to different epitopes. an evaluation of bystander activation in primary and secondary responses to viral infection.	viral infections induce extensive t cell proliferation in vivo. however, only a small fraction (1-5%) of the activated t cells have been shown to be virus specific leading to the prevailing notion that most of the t cell expansion represents cytokine-mediated by-stander activation and/or cross reactive stimulation of non specific cells. to re-examine this issue we quantitated antigen specific cd8 t cells during acute lcmv infection of mice using three sensitive techniques: (i) intracellular cyto ...	1998	9889966
the susceptibility to cytotoxic t lymphocyte mediated lysis of chemically induced sarcomas from immunodeficient and normal mice.	a panel of sarcomas induced with 3-methylcholanthrene in normal and immunodeficient mice was studied for their capacity to present antigen by the endogenous, mhc class i restricted pathway. lymphocytic choriomeningitis virus was used to infect cultured tumour cells, and the infected cells were tested for susceptibility to cytolysis by virus specific cytotoxic t cells. tumour cells originating from tumours induced in immunocompetent c.b.-17 mice presented virus antigen more efficiently than tumou ...	1997	9010497
interferon-alpha/beta inhibition of interleukin 12 and interferon-gamma production in vitro and endogenously during viral infection.	interferon (ifn)-alpha/beta-mediated negative regulation of interleukin 12 (il-12) and ifn-gamma proteins is reported here. both ifn-alpha and ifn-beta inhibited fixed staphylococcus aureus cowan strain induction of il-12 and ifn-gamma production by mouse splenic leukocytes in culture. extended studies with ifn-alpha demonstrated that inhibition was at the level of biologically active il-12 p70. effects were selective, as induction of tumor necrosis factor was unaffected and induction of il-6 wa ...	1997	9012836
protection against immunopathological consequences of a viral infection by activated but not resting cytotoxic t cells: t cell memory without "memory t cells"?	immunological memory is a key characteristic of specific immune responses. persistence of increased levels of precursor t cells is antigen-independent and is often used as an indicator of t cell memory. this study documents that, depending on the chosen readout, cytotoxic t lymphocyte (ctl) memory against lymphocytic choriomeningitis virus (lcmv) appears long- or short-lived in the absence of persisting antigen. to study t cell memory in the absence of persisting antigen, either short-lived anti ...	1997	9012837
virus-specific igd in acute viral infection of mice.	in phylogenetically diverse species with the help of t lymphocytes or soluble factors, viral infections induce the ag-specific b lymphocytes to proliferate and terminally differentiate into igm, igg, iga, igd, or ige ab-secreting cells. based on previous studies searching for igd, it was inferred that serum igd in the mouse is nearly undetectable, although in other species, e.g., humans, igd is a measurable component of serum ig. more recently, new information has been obtained indicating that i ...	1997	9013967
the discovery of mhc restriction.		1997	9018968
development of a reverse transcription-polymerase chain reaction assay for diagnosis of lymphocytic choriomeningitis virus infection and its use in a prospective surveillance study.	lymphocytic choriomeningitis virus (lcmv), which is one of several arenaviruses that are pathogenic for humans, causes encephalitis and meningitis in man. in this study, single-stage and nested reverse transcription-polymerase chain reaction (rt-pcr) assays were developed that targeted the gpc and n genes of lcmv. both assays detected < 1 tcid50 unit of lcmv. these assays were used to measure the incidence of lcmv infection by testing cerebrospinal fluid (csf) samples with > or = 10 leukocytes/m ...	1997	9021540
antiviral immune responses in ctla4 transgenic mice.	the role of b7 binding cd28 in the regulation of t- and b-cell responses against viral antigens was assessed in transgenic mice expressing soluble ctla4-hgamma1 (ctla4-ig tg mice) that blocks b7-cd28 interactions. the results indicate that transgenic soluble ctla4 does not significantly alter cytotoxic t-cell responses against replicating lymphocytic choriomeningitis virus (lcmv) or vaccinia virus but drastically impairs the induction of cytotoxic t-cell responses against abortively replicating ...	1997	9032309
a multivalent minigene vaccine, containing b-cell, cytotoxic t-lymphocyte, and th epitopes from several microbes, induces appropriate responses in vivo and confers protection against more than one pathogen.	the development of safe and effective vaccines remains a major goal in the prevention, and perhaps treatment, of infectious diseases. ideally, a single vaccine would confer protection against several pathogens and would induce both cellular and humoral arms of the immune response. we originally demonstrated that two virus-specific cytotoxic t-lymphocyte (ctl) epitopes, from the same virus but presented by different major histocompatibility complex alleles, when linked in tandem as minigenes in a ...	1997	9032365
the lassa fever virus l gene: nucleotide sequence, comparison, and precipitation of a predicted 250 kda protein with monospecific antiserum.	the large (l) rna segment of lassa fever virus (las) encodes a putative rna-dependent rna polymerase (rdrp or l protein). similar to other arenaviruses, the las l protein is encoded on the genome-complementary strand and is predicted to be 2218 amino acids in length (253 kda). it has an unusually large non-coding region adjacent to its translation start site. the las l protein contains six motifs of conserved amino acids that have been found among arenavirus l proteins and core rdrp of other seg ...	1997	9049403
virus-induced transient bone marrow aplasia: major role of interferon-alpha/beta during acute infection with the noncytopathic lymphocytic choriomeningitis virus.	the hematologic consequences of infection with the noncytopathic lymphocytic choriomeningitis virus (lcmv) were studied in wild-type mice with inherent variations in their interferon (ifn)-alpha/beta responder ability and in mutant mice lacking alpha/beta (ifn-alpha/beta r0/0) or gamma ifn (ifn-gamma r0/0) receptors. during the first week of infection, wild type mice demonstrated a transient pancytopenia. within a given genetic background, the extent of the blood cell abnormalities did not corre ...	1997	9053452
interferon-gamma is essential for destruction of beta cells and development of insulin-dependent diabetes mellitus.	autoimmune mediated destruction of beta cells of the islets of langerhans leads to insulin-dependent diabetes mellitus (iddm). rat insulin promoter (rip) lymphocytic choriomeningitis virus (lcmv) transgenic mice that express the nucleoprotein (np) or glycoprotein (gp) of lcmv under control of the rip in their beta cells develop iddm after infection with lcmv and serve as a model for virus-induced iddm. recently, kagi et al. (kagi, d., b. odermatt, p. ohashi, r.m. zinkernagel, and h. hengartner, ...	1997	9053453
use of a nonviral vector to express a chimeric trna-ribozyme against lymphocytic choriomeningitis virus: cytoplasmic accumulation of a catalytically competent transcript but minimal antiviral effect.	rna polymerase iii promoters direct the ubiquitous, high-level, expression of small, stable rnas such as trnas, and thus are attractive candidates for achieving stable expression of small therapeutic (e.g., antiviral) molecules, such as ribozymes or antisense rnas. in this article, we describe the use of a nonviral vector containing a trna promoter to express an antilymphocytic choriomeningitis virus (lcmv) ribozyme (trna-rib5). the chimeric trna-ribozyme is specifically and efficiently transcri ...	1997	9055033
anti-viral protection conferred by recombinant adenylate cyclase toxins from bordetella pertussis carrying a cd8+ t cell epitope from lymphocytic choriomeningitis virus.	the elucidation of the mechanisms of antigen presentation by major histocompatibility complex class i molecules has stimulated the search for nonreplicative vectors that could deliver cd8+ t cell epitopes to the cytosol of antigen-presenting cells to trigger the activation of specific cytotoxic t lymphocytes (ctls) in vivo. in the present study, we investigated the potential ability of an invasive adenylate cyclase toxin from bordetella pertussis, carrying a cd8+ t cell epitope from the nucleopr ...	1997	9096390
[epidemiological studies on lymphocytic choriomeningitis virus in japan].	human case of lymphocytic choriomeningitis virus (lcmv) infection was not confirmed virologically or serologically in japan. existence of the virus in experimental animals was reported in japan shortly after first isolation of lcmv in u.s.a. in japan, antibodies against lcmv and the virus were revealed in international sea ports. using gene analysis, we found lcmv bearing mice would invade into japan from south asian countries where mus musclus castaneus habitats. the antibodies against lcmv wer ...	1997	9103889
bystander activation of cytotoxic t cells: studies on the mechanism and evaluation of in vivo significance in a transgenic mouse model.	bystander activation, i.e., activation of t cells specific for an antigen x during an immune response against antigen y may occur during viral infections. however, the low frequency of bystander-activated t cells has rendered it difficult to define the mechanisms and possible in vivo relevance of this nonspecific activation. this study uses transgenic mice expressing a major histocompatibility complex class i-restricted tcr specific for glycoprotein peptide 33-41 of lymphocytic choriomeningitis ...	1997	9104811
alterations in the level of cd45 surface expression affect the outcome of thymic selection.	cd45 is a receptor protein tyrosine phosphatase whose activity is required for thymocyte development and tcr-mediated signal transduction. here we show that positive selection of tcr-alphabeta transgenic thymocytes is completely blocked in cd45 exon 6 -/- gene-deficient (cd45 -/-) mice that express the p14 tcr specific for the lymphocytic choriomeningitis virus. thymocytes from mice heterozygous for the targeted disruption of the cd45 gene (cd45 +/-) displayed a reduction in both cd45 surface in ...	1997	9120275
low-affinity cytotoxic t-lymphocytes require ifn-gamma to clear an acute viral infection.	the majority of the response of cytotoxic t-lymphocytes (ctl) to lymphocytic choriomeningitis virus (lcmv) in h-2d mice is directed toward one epitope located on the nucleoprotein (np, aa 118-126), and usually no primary responses to other epitopes are detectable. previous studies have shown that thymic expression of lymphocytic choriomeningitis virus-nucleoprotein (lcmv-np) in h-2d transgenic mice (thy-np mice) leads to deletion of high-affinity anti-lcmv-np ctl by negative selection. selection ...	1997	9126248
viral persistent infection affects both transcriptional and posttranscriptional regulation of neuron-specific molecule gap43.	recently, we reported that in vitro and in vivo persistent infection of neurons by lymphocytic choriomeningitis virus (lcmv) downregulated gap43 expression, a protein involved in neuronal plasticity associated with learning and memory. here, we investigated the transcriptional and posttranscriptional events involved. persistent lcmv infection of pc12 cells (pc12pi) caused reduced levels of gap43 steady-state mrna when compared to uninfected pc12 cells. in addition, an increase in the steady-stat ...	1997	9143270
minimal bystander activation of cd8 t cells during the virus-induced polyclonal t cell response.	acute infections with viruses such as lymphocytic choriomeningitis virus (lcmv) are associated with a massive polyclonal t cell response, but the specificities of only a small percentage of these activated t cells are known. to determine if bystander stimulation of t cells not specific to the virus plays a role in this t cell response, we examined two different systems, hy-specific t cell receptor (tcr)-transgenic mice, which have a restricted tcr repertoire, and lcmv-carrier mice, which are tol ...	1997	9151900
lymphocytic choriomeningitis virus: a new addition to the torch evaluation.		1997	9152144
multifocal defects in immune responses in relb-deficient mice.	mice with a targeted disruption of the rel/nuclear factor-kappab family member relb develop a complex inflammatory phenotype, myeloid hyperplasia, and splenomegaly due to extramedullary hemopoiesis. in this work, we report that relb-deficient mice, in addition to the pathologic changes, were highly susceptible to infection by the facultative intracellular bacterium listeria monocytogenes. relb binds transcriptionally active kappab motifs in the tnf-alpha promoter in normal cells, and in vitro st ...	1997	9164938
cytolytically active memory ctl present in lymphocytic choriomeningitis virus-immune mice after clearance of virus infection.	generally, it has been assumed that memory t cells are dormant and inactive cells in the absence of their specific ag. recent work has challenged this assumption by showing that a portion of the cd8+ memory t cell pool is in cycle. in this study, we demonstrate that a significant number of blast-size memory cd8+ t cells in mice, long after lymphocytic choriomeningitis virus (lcmv) infection, mediate cytolysis against highly sensitive targets without any in vivo or in vitro restimulation and expa ...	1997	9164957
differential immune recognition of lcmv nucleoprotein and glycoprotein in transgenic mice expressing lcmv cdna genes.	we have generated doubly transgenic (dt) mice that independently express cdna genes for the nucleocapsid protein (np) and the surface glycoproteins (gp) of lymphocytic choriomeningitis virus (lcmv). by rt-pcr, transcription of both transgenes was detected at low levels in brain and kidney but was not observed in the thymus. additionally, transcription of the gp transgene was observed in the spleen. following challenge with exogenous lcmv, an anti-np ctl response was induced in lcmv-infected dt m ...	1997	9168891
peptide antigen treatment of naive and virus-immune mice: antigen-specific tolerance versus immunopathology.	peptide-specific down-regulation of t cell responses may represent a powerful tool to intervene in autoimmune diseases or graft rejections. it is therefore important to know whether peptide treatment tolerizes both naive and antigen-experienced memory t lymphocytes. here we show that a major histocompatibility complex class i binding peptide, derived from the glycoprotein (gp33 peptide) of lymphocytic choriomeningitis virus (lcmv), specifically tolerized naive cytotoxic t lymphocytes (ctl) when ...	1997	9175830
on the key role of secondary lymphoid organs in antiviral immune responses studied in alymphoplastic (aly/aly) and spleenless (hox11(-)/-) mutant mice.	the role of the spleen and of other organized secondary lymphoid organs for the induction of protective antiviral immune responses was evaluated in orphan homeobox gene 11 knockout mice (hox11(-/-)) lacking the spleen, and in homozygous alymphoplastic mutant mice (aly/aly) possessing a structurally altered spleen but lacking lymph nodes and peyer's patches. absence of the spleen had no major effects on the immune response, other than delaying the antibody response by 1-2 d. in aly/aly mice, the ...	1997	9182687
uncovering subdominant cytotoxic t-lymphocyte responses in lymphocytic choriomeningitis virus-infected balb/c mice.	the cytotoxic t-lymphocyte response against lymphocytic choriomeningitis virus (lcmv) in balb/c mice is predominantly directed against a single, ld-restricted epitope in the viral nucleoprotein (residues 118 to 126). to investigate whether any kd/dd-restricted responses were activated but did not expand during the primary response, we used a balb/c mutant, balb/c-h-2dm2, which does not express the ld molecule. splenocytes from lcmv-infected balb/c mice were transferred into irradiated balb/c-h-2 ...	1997	9188577
functional in vivo mhc class ii loading by endogenously synthesized glycoprotein during viral infection.	mhc class ii presentation of antigenic peptides derived from soluble proteins is usually preceded by antigenic uptake via (nonreceptor-mediated) endocytosis by professional apcs, followed by processing in endosomal compartments. although in vitro alternative pathways for mhc class ii loading have been described for certain intracellularly synthesized proteins, the importance of these pathways has not been assessed in vivo. we have shown previously that endogenously produced membrane-associated g ...	1997	9190921
pathogenesis and treatment of virus-induced autoimmune diabetes: novel insights gained from the rip-lcmv transgenic mouse model.		1997	9191170
a critical role for neutralizing-antibody-producing b cells, cd4(+) t cells, and interferons in persistent and acute infections of mice with lymphocytic choriomeningitis virus: implications for adoptive immunotherapy of virus carriers.	this study demonstrates that neutralizing-antibody-producing b cells, cd4(+) t cells, and interferons (ifns) are of key importance in virus control both in adoptive immunotherapy of persistent infection and in the late phase of acute infection with the we strain of lymphocytic choriomeningitis virus (lcmv). we report the following results. (i) clearance of lcmv-we from c57bl/6 carrier mice by adoptive transfer of memory spleen cells requires b cells and cd4(+) t cells but not necessarily cd8(+) ...	1997	9192659
congenital lymphocytic choriomeningitis virus syndrome: a disease that mimics congenital toxoplasmosis or cytomegalovirus infection.	to describe the clinical characteristics of intrauterine infection with lymphocytic choriomeningitis (lcm) virus, an uncommonly recognized cause of congenital viral infection.	1997	9200383
recombinant parvovirus-like particles as an antigen carrier: a novel nonreplicative exogenous antigen to elicit protective antiviral cytotoxic t cells.	to develop a strategy that promotes efficient antiviral immunity, hybrid virus-like particles (vlp) were prepared by self-assembly of the modified porcine parvovirus vp2 capsid protein carrying a cd8(+) t cell epitope from the lymphocytic choriomeningitis virus nucleoprotein. immunization of mice with these hybrid pseudoparticles, without adjuvant, induced strong cytotoxic t lymphocyte (ctl) responses against both peptide-coated- or virus-infected-target cells. this cd8(+) class i-restricted cyt ...	1997	9207121
sensitization to lipopolysaccharide in mice with asymptomatic viral infection: role of t cell-dependent production of interferon-gamma.	the interplay between viral infection and lipopolysaccharide (lps) was studied. infection with a noncytopathogenic virus, lymphocytic choriomeningitis virus (lcmv), was found to sensitize mice to low doses of lps. in vivo, this hypersensitivity correlated with hyperproduction of tumor necrosis factor-alpha (tnf-alpha), and in vitro, lps-stimulated splenic adherent cells produced increased amounts of tnf-alpha. hyperproduction of tnf-alpha was temporally correlated with virus-induced production o ...	1997	9207361