Publications

increased expression of the nk cell receptor klrg1 by virus-specific cd8 t cells during persistent antigen stimulation.	the killer cell lectin-like receptor g1 (klrg1) is a natural killer cell receptor expressed by t cells that exhibit impaired proliferative capacity. here, we determined the klrg1 expression by virus-specific t cells. we found that repetitive and persistent antigen stimulation leads to an increase in klrg1 expression of virus-specific cd8+ t cells in mice and that virus-specific cd8+ t cells are mostly klrg1+ in chronic human viral infections (human immunodeficiency virus, cytomegalovirus, and ep ...	2005	16140789
islet-specific expression of cxcl10 causes spontaneous islet infiltration and accelerates diabetes development.	during inflammation, chemokines are conductors of lymphocyte trafficking. the chemokine cxcl10 is expressed early after virus infection. in a virus-induced mouse model for type 1 diabetes, cxcl10 blockade abrogated disease by interfering with trafficking of autoaggressive lymphocytes to the pancreas. we have generated transgenic rat insulin promotor (rip)-cxcl10 mice expressing cxcl10 in the beta cells of the islets of langerhans to evaluate how bystander inflammation influences autoimmunity. ri ...	2005	16148094
virus-induced inhibition of cd1d1-mediated antigen presentation: reciprocal regulation by p38 and erk.	a critical component of the host's innate immune response involves lipid ag presentation by cd1d molecules to nk t cells. in this study we used murine cd1d1-transfected l (l-cd1) cells to study the effect of viruses on cd1d-mediated ag presentation to nkt cells and found that an infection with vesicular stomatitis and vaccinia (but not lymphocytic choriomeningitis) virus inhibited murine cd1d1-mediated ag presentation. this was under the reciprocal control of the mapks, p38 and erk, and was due ...	2005	16177070
recall proliferation potential of memory cd8+ t cells and antiviral protection.	memory cd8+ t cells play a crucial role in mediating protection from infection with viruses and other intracellular pathogens. memory t cells are not a homogenous cellular population and may be separated into central memory t cells with substantial recall proliferation capacity and effector memory t cells with limited recall proliferation capacity. it has been suggested that the protective capacity of effector memory t cells is more limited than that of central memory t cells in viral infections ...	2005	16177115
functional properties and lineage relationship of cd8+ t cell subsets identified by expression of il-7 receptor alpha and cd62l.	three major subsets of ag-experienced cd8+ t cells have been identified according to their expression of cd62l and cd127. these markers are associated with central memory t cells (cd62l+ cd127+), effector memory t cells (cd162l- cd127+), and effector t cells (cd62l- cd127-). in this study we characterized the development of these three populations during acute and chronic viral infections and after immunization with virus-like particles and determined their lineage relation and functional and pr ...	2005	16177116
innate signals compensate for the absence of pkc-{theta} during in vivo cd8(+) t cell effector and memory responses.	pkc- is central to t-helper (th) 2 cell differentiation and effector function; however, its importance for antiviral effector, and in particular memory cd8(+) t cell responses, remains unclear. we have investigated the role of pkc- during in vivo and in vitro responses against influenza virus, lymphocytic choriomeningitis virus, vaccinia virus, and replication-deficient virus-like particles. in the absence of pkc-, antiviral cd8(+) t cells presented an unresponsive phenotype in vitro, which coul ...	2005	16186501
rapid recruitment of virus-specific cd8 t cells restructures immunodominance during protective secondary responses.	in this study we investigate the attributes of virus-specific memory cd8 t cells which most effectively control secondary infections. by rechallenging mice that had cleared primary lymphocytic choriomeningitis virus infections, we revealed that the secondary response is remarkably swift. within 6 h following secondary infection, the production of gamma interferon becomes detectable directly ex vivo. during this protective phase of the secondary response, a very early elaboration of effector acti ...	2005	16188973
development of multiplex pcrs for detection of common viral pathogens and agents of congenital infections.	potential causes of congenital infection include toxoplasma gondii and viruses such as cytomegalovirus (cmv), enterovirus, hepatitis c virus, herpes simplex virus types 1 and 2 (hsv-1 and -2), human herpesvirus types 6, 7, and 8, lymphocytic choriomeningitis virus, parvovirus, rubella virus, and varicella-zoster virus. testing for each of these agents using nucleic acid tests is time consuming and the availability of clinical samples such as amniotic fluid or neonatal blood is often limited. the ...	2005	16207970
rapid production of tnf-alpha following tcr engagement of naive cd8 t cells.	the acquisition of effector functions by naive cd8 t cells following tcr engagement is thought to occur sequentially with full functionality being gained only after the initiation of division. we show that naive cd8 t cells are capable of immediate effector function following tcr engagement, which stimulates the rapid production of tnf-alpha. stimulation of splenocytes from naive mice of differing genetic backgrounds with anti-cd3epsilon mab resulted in significant production of tnf-alpha by nai ...	2005	16210607
requirement for neutralizing antibodies to control bone marrow transplantation-associated persistent viral infection and to reduce immunopathology.	bone marrow transplantation (bmt) is commonly used in the treatment of leukemia, however its therapeutic application is partly limited by the high incidence of associated opportunistic infections. we modeled this clinical situation by infecting mice that underwent bmt with lymphocytic choriomeningitis virus (lcmv) and investigated the potential of immunotherapeutic strategies to counter such infections. all mice that received bmt survived lcmv infection and developed a virus carrier status. immu ...	2005	16210661
transduction of human glial and neuronal tumor cells with different lentivirus vector pseudotypes.	lentiviral vectors have proven to be valuable tools for in vitro and in vivo gene delivery because they can transduce dividing and non-dividing cells efficiently, and mediate long-term gene expression. pseudotyping of lentiviral vectors with envelope proteins other than vsv-g has resulted in enhanced transduction of certain cell types and tissues. in order to improve lentiviral vector-based gene therapy for peripheral neuroectodermal and brain tumors, we compared the efficiency of eight differen ...	2004	15662969
ip-10 and type 1 diabetes: a question of time and location.	chemokines are key signal molecules that attract cells of the host immune system to the site of a potential threat. virus infections usually induce a massive chemokine and cytokine burst and therefore recruit a large plethora of leukocytes to the site of infection with the goal to restrict and abrogate viral spread. the down side of this massive excitation of the human defense system is non-specific activation of potentially self-reactive lymphocytes. coupled with an antigen-specific event, for ...	2004	15672495
the contraction phase of virus-specific cd8+ t cells is unaffected by a pan-caspase inhibitor.	the effectiveness of protection conferred by cd8(+) memory t cells is determined by both their quality and their quantity, which suggests that vaccine efficacy might be improved if it were possible to increase the size of the memory pool. approximately 90% of virus-specific cd8(+) t cells die during the contraction phase and, herein, we have attempted to increase the memory pool by reducing cd8(+) t cell death. cd8(+) t cell contraction has been attributed to apoptosis, or programmed cell death ...	2004	15557151
impact of ccr7 on priming and distribution of antiviral effector and memory ctl.	the chemokine receptor ccr7 is a key factor in the coordinate migration of t cells and dendritic cells (dc) into and their localization within secondary lymphoid organs. in this study we investigated the impact of ccr7 on cd8(+) t cell responses by infecting ccr7(-/-) mice with lymphocytic choriomeningitis virus (lcmv). we found that the absence of ccr7 affects the magnitude of an antiviral ctl response during the acute phase, with reduced numbers of virus-specific ctl in all lymphoid and nonlym ...	2004	15557160
activation of virus-specific cd8+ t cells by lipopolysaccharide-induced il-12 and il-18.	virus-specific t cells represent a hallmark of ag-specific, adaptive immunity. however, some t cells also demonstrate innate functions, including non-ag-specific ifn-gamma production in response to microbial products such as lps or exposure to il-12 and/or il-18. in these studies we examined lps-induced cytokine responses of cd8(+) t cells directly ex vivo. following acute viral infection, 70-80% of virus-specific t cells will produce ifn-gamma after exposure to lps-induced cytokines, and neutra ...	2004	15557182
cure of prediabetic mice by viral infections involves lymphocyte recruitment along an ip-10 gradient.	viruses can cause but can also prevent autoimmune disease. this dualism has certainly hampered attempts to establish a causal relationship between viral infections and type 1 diabetes (t1d). to develop a better mechanistic understanding of how viruses can influence the development of autoimmune disease, we exposed prediabetic mice to various viral infections. we used the well-established nod and transgenic rip-lcmv models of autoimmune diabetes. in both cases, infection with the lymphocytic chor ...	2004	14702111
effects of an epitope-specific cd8+ t-cell response on murine coronavirus central nervous system disease: protection from virus replication and antigen spread and selection of epitope escape mutants.	both cd4(+) and cd8(+) t cells are required for clearance of the murine coronavirus mouse hepatitis virus (mhv) during acute infection. we investigated the effects of an epitope-specific cd8(+) t-cell response on acute infection of mhv, strain a59, in the murine cns. mice with cd8(+) t cells specific for gp33-41 (an h-2d(b)-restricted cd8(+) t-cell epitope derived from lymphocytic choriomeningitis glycoprotein) were infected with a recombinant mhv-a59, also expressing gp33-41, as a fusion protei ...	2004	14722270
gene-gun dna vaccination aggravates respiratory syncytial virus-induced pneumonitis.	a cd8+ t-cell memory response to respiratory syncytial virus (rsv) was generated by using a dna vaccine construct encoding the dominant kd-restricted epitope from the viral transcription anti-terminator protein m2 (m2(82-90)), linked covalently to human beta2-microglobulin (beta2m). cutaneous gene-gun immunization of balb/c mice with this construct induced an antigen-specific cd8+ t-cell memory. after intranasal rsv challenge, accelerated cd8+ t-cell responses were observed in pulmonary lymph no ...	2004	15448365
enhanced expression of cell cycle regulatory genes in virus-specific memory cd8+ t cells.	unlike naive cd8+ t cells, antigen-experienced memory cd8+ t cells persist over time due to their unique ability to homeostatically proliferate. it was hypothesized that memory cells might differentially regulate the expression of genes that control the cell cycle to facilitate homeostatic proliferation. to test this, the expression levels of 96 different cell cycle regulatory genes were compared between transgenic naive and memory cd8+ t cells that specifically recognize the gp33-41 epitope of ...	2004	15452215
antioxidant treatment reduces expansion and contraction of antigen-specific cd8+ t cells during primary but not secondary viral infection.	during many viral infections, antigen-specific cd8(+) t cells undergo large-scale expansion. after viral clearance, the vast majority of effector cd8(+) t cells undergo apoptosis. previous studies have implicated reactive oxygen intermediates (roi) in lymphocyte apoptosis. the purpose of the experiments presented here was to determine the role of roi in the expansion and contraction of cd8(+) t cells in vivo during a physiological response such as viral infection. mice were infected with lymphoc ...	2004	15452243
myristoylation of the ring finger z protein is essential for arenavirus budding.	the arenavirus small ring finger z protein is the main driving force of arenavirus budding. the primary structure of z is devoid of hydrophobic transmembrane domains, but both lymphocytic choriomeningitis virus (lcmv) and lassa fever virus z proteins accumulate near the inner surface of the plasma membrane and are strongly membrane associated. all known arenavirus z proteins contain a glycine (g) at position 2, which is a potential acceptor site for a myristoyl moiety. metabolic labeling showed ...	2004	15452271
tcr affinity and negative regulation limit autoimmunity.	autoimmune diseases are often mediated by self-reactive t cells, which must be activated to cause immunopathology. one mechanism, known as molecular mimicry, proposes that self-reactive t cells may be activated by pathogens expressing crossreactive ligands. here we have developed a model to investigate how the affinity of the t-cell receptor (tcr) for the activating agent influences autoimmunity. our model shows that an approximately fivefold difference in the tcr affinity for the activating lig ...	2004	15467726
kinetics of protective antibodies are determined by the viral surface antigen.	delayed and weak virus neutralizing antibody (nab) responses represent a hallmark correlating not only with the establishment of persistent infection but also with unsuccessful vaccine development. using a reverse genetic approach, we evaluated possible underlying mechanisms in 2 widely studied viral infection models. swapping the glycoproteins (gps) of lymphocytic choriomeningitis virus (lcmv, naturally persisting, noncytolytic, inefficient nab inducer) and vesicular stomatitis virus (vsv, nonp ...	2004	15467838
rebuilding an immune-mediated central nervous system disease: weighing the pathogenicity of antigen-specific versus bystander t cells.	although both self- and pathogen-specific t cells can participate in tissue destruction, recent studies have proposed that after viral infection, bystander t cells of an irrelevant specificity can bypass peptide-mhc restriction and contribute to undesired immunopathological consequences. to evaluate the importance of this mechanism of immunopathogenesis, we determined the relative contributions of ag-specific and bystander cd8+ t cells to the development of cns disease. using lymphocytic choriom ...	2004	15470017
preapoptotic phenotype of viral epitope-specific cd8 t cells precludes memory development and is an intrinsic property of the epitope.	virus-specific cd8 t cells after clearance of infection reduce their number in lymphoid organs by apoptotic death and by migration into peripheral tissues. during and after infection, many lymphocytic choriomeningitis virus (lcmv)-specific cd8 t cells in lymphoid but not peripheral tissues are in a preapoptotic state, as detected by the early apoptosis marker annexin v. in this report, we investigated the significance of this preapoptotic state and how it may be influenced by viral epitope speci ...	2004	15470058
[screening for antibodies against zoonotic agents among employees of the zoological garden of vienna, schönbrunn, austria].	the aim of this study was to investigate the prevalence of antibodies against zoonotic agents in employees of the zoological garden of vienna, schönbrunn, austria. sixty out of 120 employees participated in the study. in 97% of them antibodies to at least one zoonotic agent were identified. only two participants were free of antibodies to the zoonotic agents tested. the following seroprevalences (in brackets) were obtained: viral zoonotic (and potentially zoonotic) agents: influenzavirus a/h1n1 ...	2004	15495931
antigen-independent memory cd8 t cells do not develop during chronic viral infection.	memory t cells can persist for extended periods in the absence of antigen, and long-term t cell immunity is often seen after acute infections. paradoxically, there have been observations suggesting that t cell memory may be antigen-dependent during chronic infections. to elucidate the underlying mechanisms we have compared memory cd8 t cell differentiation during an acute versus chronic infection by using the mouse model of infection with lymphocytic choriomeningitis virus. we found that during ...	2004	15505208
perforin and fas act together in the induction of apoptosis, and both are critical in the clearance of lymphocytic choriomeningitis virus infection.	in this report we questioned the current view that the two principal cytotoxic pathways, the exocytosis and the fas ligand (fasl)/fas-mediated pathway, have largely nonoverlapping biological roles. for this purpose we have analyzed the response of mice that lack fas as well as granzyme a (gzma) and gzmb (fasxgzmaxb(-/-)) to infection with lymphocytic choriomeningitis virus (lcmv). we show that fasxgzmaxb(-/-) mice, in contrast to b6, fas(-/-), and gzmaxb(-/-) mice, do not recover from a primary ...	2004	15507626
single-epitope dna vaccination prevents exhaustion and facilitates a broad antiviral cd8+ t cell response during chronic viral infection.	induction of a monospecific antiviral cd8+ t cell response may pose a risk to the host due to the narrow t cell response induced. at the individual level, this may result in selection of cd8+ t cell escape variants, particularly during chronic viral infection. second, prior immunization toward a single dominant epitope may suppress the response to other viral epitopes, and this may lead to increased susceptibility to reinfection with escape variants circulating in the host population. to address ...	2004	15528367
bone marrow plasmacytoid dendritic cells can differentiate into myeloid dendritic cells upon virus infection.	two subsets of dendritic cell (dcs), plasmacytoid (p) and myeloid (m) dcs, have been described in humans and mice. these subsets are known to have divergent roles during an immune response, but their developmental course is unclear. here we report that virus infection induces bone marrow pdcs to differentiate into mdcs, thereby undergoing profound phenotypic and functional changes including the acquisition of enhanced antigen-presenting capacity and the ability to recognize different microbial s ...	2004	15531885
role of isg15 protease ubp43 (usp18) in innate immunity to viral infection.	innate immune responses provide the host with an early protection barrier against infectious agents, including viruses, and help shape the nature and quality of the subsequent adaptive immune responses of the host. expression of isg15 (ucrp), a ubiquitin-like protein, and protein isgylation are highly increased upon viral infection. we have identified ubp43 (usp18) as an isg15 deconjugating protease. protein isgylation is enhanced in cells deficient in ubp43 (ref. 6). here we have examined the r ...	2004	15531891
optimized large-scale production of high titer lentivirus vector pseudotypes.	the goal of the present study was to develop an efficient transient transfection method for large-scale production of high titer lentivirus vector stocks of eight different pseudotypes. the envelope genes used for this purpose were those from vsv-g, mokola, rabies, mlv-ampho, mlv-10a1, lcmv-we, and lcmv-arm53b. all envelopes were cloned into phcmv, which yielded lentivirus vector titers one, two, or three orders of magnitude higher than the original plasmids for the rabies, mlv-10a1, and mlv-amp ...	2004	15542136
effect of chronic viral infection on epitope selection, cytokine production, and surface phenotype of cd8 t cells and the role of ifn-gamma receptor in immune regulation.	regulation of cd8 t cell responses in chronic viral infections is not well understood. in this study, we have compared the cd8 t cell responses to immunodominant and subdominant epitopes during an acute and a chronic lymphocytic choriomeningitis virus (lcmv) infection in mice. the epitope hierarchy of the primary cd8 t cell response was similar in acute and chronic lcmv infections. however, strikingly, the epitope hierarchy of the primary cd8 t cell response was conserved in the t cell memory on ...	2004	14734726
ifn-gamma promotes fas ligand- and perforin-mediated liver cell destruction by cytotoxic cd8 t cells.	to study liver cell damage by ctl, cd8 t cells from p14 tcr transgenic (tg) mice specific for the gp33 epitope of lymphocytic choriomeningitis virus with either deficiency in ifn-gamma (p14.ifn-gamma(null)), functional fas ligand (p14.gld), or perforin (p14.pko) were transferred into h8 tg mice ubiquitously expressing gp33 ag. treatment of h8 recipient mice with agonistic anti-cd40 abs induced vigorous expansion of the transferred p14 t cells and led to liver cell destruction determined by incre ...	2004	14734739
nonmethylated cg motifs packaged into virus-like particles induce protective cytotoxic t cell responses in the absence of systemic side effects.	dna rich in nonmethylated cg motifs (cpgs) greatly facilitates induction of immune responses against coadministered ags. cpgs are therefore among the most promising adjuvants known to date. nevertheless, cpgs are characterized by two drawbacks. they have unfavorable pharmacokinetics and may exhibit systemic side effects, including splenomegaly. we show in this study that packaging cpgs into virus-like particles (vlps) derived from the hepatitis b core ag or the bacteriophage qbeta is a simple an ...	2004	14734761
plasticity of t cell memory responses to viruses.	virus-specific memory t cell populations demonstrate plasticity in antigenic and functional phenotype, in recognition of antigen, and in their ability to accommodate new memory t cell populations. the adaptability of complex antigen-specific t cell repertoires allows the host to respond to a diverse array of pathogens and accommodate memory pools to many pathogens in a finite immune system. this is in part accounted for by crossreactive memory t cells, which can be employed in immune responses a ...	2004	14738760
transduction patterns of pseudotyped lentiviral vectors in the nervous system.	we have developed a non-primate-based lentiviral vector based on the equine infectious anemia virus (eiav) for efficient gene transfer to the central and peripheral nervous systems. previously we have demonstrated that pseudotyping lentiviral vectors with the rabies virus glycoprotein confers retrograde axonal transport to these vectors. in the present study we have successfully produced high-titer eiav vectors pseudotyped with envelope glycoproteins from rhabdovirus vesicular stomatitis virus ( ...	2004	14741783
mucosal arenavirus infection of primates can protect them from lethal hemorrhagic fever.	arenaviruses are transmitted from rodents to human beings by blood or mucosal exposure. the most devastating arenavirus in terms of human disease is lassa fever virus, causing up to 300,000 annual infections in west africa. we used a model for lassa fever in which rhesus macaques were infected with a related virus, lymphocytic choriomeningitis virus (lcmv). our goals were to determine the outcome of infection after mucosal inoculation and later lethal challenge, to characterize protective immune ...	2004	14748066
commentary: t cells get by with a little help from their friends.	in animal models, lymphocytic choriomeningitis virus (lcmv) may be controlled after acute infection or may establish various levels of persistence. cytotoxic responses mediated by cd8(+) t cells are responsible for both initial control of lcmv and for immunopathology. as discussed in this article, there is emerging evidence that the levels of antigen to which the immune system is exposed over time are important in controlling cd8(+) t cell activation, memory responses and exhaustion, and that th ...	2004	14768035
maintenance of memory ctl responses by t helper cells and cd40-cd40 ligand: antibodies provide the key.	cytotoxic t lymphocytes (ctl) are essential for control of primary infections by many pathogens and in particular by non-cytopathic viruses. it has been proposed that long-term maintenance of ctl memory and control of lymphocytic choriomeningitis virus (lcmv) is dependent upon the presence of t helper cells and interaction of antigen-presenting cells and ctl via cd40 and its ligand cd40l. however, we demonstrate here that cd40-cd40l interaction maintains ctl memory by induction of virus-specific ...	2004	14768036
underwhelming the immune response: effect of slow virus growth on cd8+-t-lymphocyte responses.	the speed of virus replication has typically been seen as an advantage for a virus in overcoming the ability of the immune system to control its population growth. under some circumstances, the converse may also be true: more slowly replicating viruses may evoke weaker cellular immune responses and therefore enhance their likelihood of persistence. using the model of lymphocytic choriomeningitis virus (lcmv) infection in mice, we provide evidence that slowly replicating strains induce weaker cyt ...	2004	14963121
expansion of protective cd8+ t-cell responses driven by recombinant cytomegaloviruses.	cd8(+) t cells are critical for the control of many persistent viral infections, such as human immunodeficiency virus, hepatitis c virus, epstein-barr virus, and cytomegalovirus (cmv). in most infections, large cd8(+)-t-cell populations are induced early but then contract and are maintained thereafter at lower levels. in contrast, cd8(+) t cells specific for murine cmv (mcmv) have been shown to gradually accumulate after resolution of primary infection. this unique behavior is restricted to cert ...	2004	14963122
transduction of human islets with pseudotyped lentiviral vectors.	type i diabetes is caused by an autoimmune-mediated elimination of insulin-secreting pancreatic islets. genetic modification of islets offers a powerful molecular tool for improving our understanding of islet biology. moreover, efficient genetic engineering of islets could allow for evaluation of new strategies aimed at preventing islet destruction. the present study evaluated the ability of a human immunodeficiency virus (hiv)-based lentiviral vector pseudotyped with various viral envelopes to ...	2004	14975193
cd4 t cell-dependent cd8 t cell maturation.	we have investigated the contribution of cd4 t cells to the optimal priming of functionally robust memory cd8 t cell subsets. intranasal infection of cd4 t cell-deficient (cd4(-/-)) mice with lymphocytic choriomeningitis virus resulted in the elaboration of virus-specific cd8 t cell responses that cleared the infection. however, by comparison with normal mice, the virus-specific cd8 t cells in cd4(-/-) mice were quantitatively and qualitatively different. in normal mice, lymphocytic choriomening ...	2004	14978084
comprehensive early and lasting loss of memory cd8 t cells and functional memory during acute and persistent viral infections.	viral infections have been shown to induce lymphopenias that lower memory cd8 t cell frequencies, and they also have been shown to cause a permanent loss of memory cells specific to previously encountered pathogens. in this study, the patterns and significance of virus-induced memory cd8 t cell depletion were examined in mice immune to heterologous (pichinde, vesicular stomatitis, vaccinia) viruses and subsequently challenged with acute or persistent lymphocytic choriomeningitis virus infections ...	2004	14978120
very diverse cd8 t cell clonotypic responses after virus infections.	we measured cd8 t cell clonotypic diversity to three epitopes recognized in c57bl/6 mice infected with mouse hepatitis virus, strain jhm, or lymphocytic choriomeningitis virus. we isolated epitope-specific t cells with an ifn-gamma capture assay or mhc class i/peptide tetramers and identified different clonotypes by vbeta chain sequence analysis. in agreement with our previous results, the number of different clonotypes responding to all three epitopes fit a log-series distribution. from these d ...	2004	14978121
virally induced inflammation triggers fratricide of fas-ligand-expressing beta-cells.	tissue-specific expression of fas-ligand (fas-l) can provide immune privilege by inducing apoptosis of "invading" lymphocytes expressing fas. however, accelerated diabetes has been reported in transgenic mice expressing fas-l in islets (rip-fas-l) as a result of fas-dependent fratricide of beta-cells after transfer of diabetogenic clones. here we studied whether fas-l could protect islets from autoaggressive cd8 lymphocytes in a transgenic model of virally induced diabetes (rip-lcmv-np transgeni ...	2004	14988242
cells expressing the ring finger z protein are resistant to arenavirus infection.	arenaviruses include lassa fever virus (lfv) and the south american hemorrhagic fever viruses. these viruses cause severe human disease, and they pose a threat as agents of bioterrorism. arenaviruses are enveloped viruses with a bisegmented negative-strand rna genome whose proteomic capability is limited to four polypeptides: nucleoprotein (np); surface glycoprotein (gp), which is proteolytically processed into gp1 and gp2; polymerase (l); and a small (11-kda) ring finger protein (z). our invest ...	2004	14990716
inhibition of different lassa virus strains by alpha and gamma interferons and comparison with a less pathogenic arenavirus.	the high pathogenicity of lassa virus is assumed to involve resistance to the effects of interferon (ifn). we have analyzed the effects of alpha ifn (ifn-alpha), ifn-gamma, and tumor necrosis factor alpha (tnf-alpha) on replication of lassa virus compared to the related, but less pathogenic, lymphocytic choriomeningitis virus (lcmv). three low-passage lassa virus strains (av, nl, and csf), isolated from humans with mild to fulminant lassa fever, were tested. lassa virus replication was inhibited ...	2004	14990737
viral immunosuppression: disabling the guards.	when facing an immune response, viruses can either attempt to elude them or confront them. a new report demonstrates that a lymphocytic choriomeningitis virus (lcmv) strain can suppress immune responses by targeting both development and activation of dcs. ironically, type i ifn released in response to lcmv infection contributes to the blockade of dc development. the discovery of these immunosuppressive mechanisms provides new perspectives for the therapy of chronic infections associated with imm ...	2004	14991061
viral targeting of hematopoietic progenitors and inhibition of dc maturation as a dual strategy for immune subversion.	dcs play a pivotal role in bringing forth innate and adaptive immune responses. viruses can specifically target dcs, rendering them ineffective in stimulating t cells, which can ultimately lead to immunosuppression. in the present study we have identified several potential mechanisms by which lymphocytic choriomeningitis virus (lcmv) induces immunosuppression in its natural murine host. the immunosuppressive lcmv variant clone 13 (cl 13) infects dcs and interferes with their maturation and antig ...	2004	14991072
influence of flanking sequences on presentation efficiency of a cd8+ cytotoxic t-cell epitope delivered by parvovirus-like particles.	we have previously developed an antigen-delivery system based on hybrid recombinant porcine parvovirus-like particles (ppv-vlps) formed by the self-assembly of the vp2 protein of ppv carrying a foreign epitope at its n terminus. in this study, different constructs were made containing a cd8(+) t-cell epitope of chicken ovalbumin (ova) to analyse the influence of the sequence inserted into vp2 on the correct processing of vlps by antigen-presenting cells. we analysed the presentation of the ova e ...	2004	14993639
cutting edge: long-lived cd8 memory and protective immunity in the absence of cd40 expression on cd8 t cells.	cd8 t cells need cd4 t cells to develop into long-lived, functional memory cells that provide protection against pathogen rechallenge. we investigated whether signaling via cd40 expressed on the cd8 cells themselves is involved in this cooperation. in murine responses to listeria monocytogenes and lymphocytic choriomeningitis virus, we found no evidence of any requirement for cd40-cd40 ligand interaction at this level. no differences were observed between cd40(-/-) and cd40(+/+) cd8 t cells that ...	2004	15004136
cd1d1-dependent control of the magnitude of an acute antiviral immune response.	cd1d1-restricted nk t (nkt) cells rapidly secrete both th1 and th2 cytokines upon activation and are therefore thought to play a regulatory role during an immune response. in this study we examined the role of cd1d1 molecules and nkt cells in regulating virus-induced cytokine production. cd1d1-deficient (cd1ko) mice, which lack nkt cells, were infected with lymphocytic choriomeningitis virus, and spontaneous cytokine release from splenocytes was measured. we found that cd1ko mice produce signifi ...	2004	15004145
differential tissue-specific regulation of antiviral cd8+ t-cell immune responses during chronic viral infection.	the hallmarks of the immune response to viral infections are the expansion of antigen-specific cd8(+) cytotoxic t lymphocytes (ctls) after they encounter antigen-presenting cells in the lymphoid tissues and their subsequent redistribution to nonlymphoid tissues to deal with the pathogen. control mechanisms exist within ctl activation pathways to prevent inappropriate ctl responses against disseminating infections with a broad distribution of pathogen in host tissues. this is demonstrated during ...	2004	15016881
old and new world arenaviruses share a highly conserved epitope in the fusion domain of the glycoprotein 2, which is recognized by lassa virus-specific human cd4+ t-cell clones.	data from human studies and animal experiments indicate a dominant role of t-cells over antibodies in controlling acute lassa virus infection and providing immunity to reinfection. knowledge of the epitopes recognized by t-cells may therefore be crucial to the development of a recombinant lassa virus vaccine. in order to study human t-cell reactivity to the most conserved structural protein of lassa virus, the glycoprotein 2 (gp2), seven gp2-specific cd4+ t-cell clones (tccs) were generated from ...	2004	15033572
virus-induced activation of self-specific tcr alpha beta cd8 alpha alpha intraepithelial lymphocytes does not abolish their self-tolerance in the intestine.	tcralphabeta cd8alphaalpha intestinal intraepithelial lymphocytes (iel) represent an enigmatic subset of t cells, particularly, in regard to their potential functions and the apparent persistence of cells expressing self-specific tcr. we have used mice that are transgenic for the tcralphabeta specific for the lymphocytic choriomeningitis virus (lcmv)-derived peptide gp33, and tcralphabeta-transgenic mice that coexpress the gp33 ag ubiquitously, to analyze the functional properties of tcralphabet ...	2004	15034030
maintenance, loss, and resurgence of t cell responses during acute, protracted, and chronic viral infections.	the acute phase of many viral infections is associated with the induction of a pronounced cd8 t cell response which plays a principle role in clearing the infection. by contrast, certain infections are not as readily controlled. in this study, we have used the well-defined system of lymphocytic choriomeningitis virus (lcmv) infection of mice to determine quantitative and qualitative changes in virus-specific cd8 t cell responses that rapidly resolve acute infections, more slowly control protract ...	2004	15034033
dissection of antiviral and immune regulatory functions of tumor necrosis factor receptors in a chronic lymphocytic choriomeningitis virus infection.	the effector function of cd8 t cells is mediated via cell-mediated cytotoxicity and production of cytokines like gamma interferon (ifn-gamma) and tumor necrosis factor alpha (tnf-alpha). while the roles of perforin-dependent cytotoxicity, ifn-gamma, and tnf-alpha in controlling acute viral infections are well studied, their relative importance in defense against chronic viral infections is not well understood. using mice deficient for tnf receptor (tnfr) i and/or ii, we show that tnf-tnfr intera ...	2004	15047807
immediate cytotoxicity but not degranulation distinguishes effector and memory subsets of cd8+ t cells.	cd8+ t cells play a central role in the resolution and containment of viral infections. a key effector function of cd8+ t cells is their cytolytic activity toward infected cells. here, we studied the regulation of cytolytic activity in naive, effector, and central versus effector memory cd8+ t cells specific for the same glycoprotein-derived epitope of lymphocytic choriomeningitis virus. our results show that the kinetics of degranulation, assessed by a novel flow cytometric based assay, were id ...	2004	15051762
complexity of cnc transcription factors as revealed by gene targeting of the nrf3 locus.	cap'n'collar (cnc) family basic leucine zipper transcription factors play crucial roles in the regulation of mammalian gene expression and development. to determine the in vivo function of the cnc protein nrf3 (nf-e2-related factor 3), we generated mice deficient in this transcription factor. we performed targeted disruption of two nrf3 exons coding for cnc homology, basic dna-binding, and leucine zipper dimerization domains. nrf3 null mice developed normally and revealed no obvious phenotypic d ...	2004	15060151
an animal model of hemophagocytic lymphohistiocytosis (hlh): cd8+ t cells and interferon gamma are essential for the disorder.	hemophagocytic lymphohistiocytosis (hlh) is a rare disorder with familial and acquired forms. the familial form is associated with mutations in the perforin gene and both forms are associated with severe defects in lymphocyte cytotoxic function. we examined perforin-deficient mice as a model of hlh in order to gain insight into this poorly understood disorder. while these mice do not spontaneously develop hlh-like symptoms, we found that they manifest all of the features of hlh after infection w ...	2004	15069016
do thymically and strictly extrathymically developing t cells generate similar immune responses?	if present in sufficient numbers, could extrathymic t cells substitute for thymus-derived t cells? to address this issue, we studied extrathymic t cells that develop in athymic mice under the influence of oncostatin m (om). in this model, extensive t-cell development is probably due to amplification of a minor pathway of t-cell differentiation taking place only in the lymph nodes. extrathymic cd4 t cells expanded poorly and were deficient in providing b-cell help after infection with vesicular s ...	2004	15070691
a stochastic model of cytotoxic t cell responses.	we have constructed a stochastic stage-structured model of the cytotoxic t lymphocyte (ctl) response to antigen and the maintenance of immunological memory. the model follows the dynamics of a viral infection and the stimulation, proliferation, and differentiation of naïve cd8(+) t cells into effector ctl, which can eliminate virally infected cells. the model is capable of following the dynamics of multiple t cell clones, each with a t cell receptor represented by a digit string. mhc-viral pepti ...	2004	15094017
t-bet controls autoaggressive cd8 lymphocyte responses in type 1 diabetes.	the t-box transcription factor t-bet is known to control lineage commitment and interferon-gamma production by t helper 1 (th1) cd4 lymphocytes. we report here that t-bet is essential for development of cd8 lymphocyte-dependent autoimmune diabetes (type 1 diabetes [t1d]) in the rat insulin promoter-lymphocytic choriomeningitis virus (lcmv) transgenic model for virally induced t1d. in the absence of t-bet, autoaggressive (anti-lcmv) cd8 lymphocytes were reduced in number and produced less ifn-gam ...	2004	15096540
determination of structural principles underlying three different modes of lymphocytic choriomeningitis virus escape from ctl recognition.	lymphocytic choriomeningitis virus infection of h-2(b) mice generates a strong cd8(+) ctl response mainly directed toward three immunodominant epitopes, one of which, gp33, is presented by both h-2d(b) and h-2k(b) mhc class i molecules. this ctl response acts as a selective agent for the emergence of viral escape variants. these variants generate altered peptide ligands (apls) that, when presented by class i mhc molecules, antagonize ctl recognition and ultimately allow the virus to evade the ce ...	2004	15100292
immunology. cd8alphaalpha and t cell memory.		2004	15105485
cd8alphaalpha-mediated survival and differentiation of cd8 memory t cell precursors.	memory t cells are long-lived antigen-experienced t cells that are generally accepted to be direct descendants of proliferating primary effector cells. however, the factors that permit selective survival of these t cells are not well established. we show that homodimeric alpha chains of the cd8 molecule (cd8alphaalpha) are transiently induced on a selected subset of cd8alphabeta+ t cells upon antigenic stimulation. these cd8alphaalpha molecules promote the survival and differentiation of activat ...	2004	15105501
suppressing the suppressors.		2004	15109942
does toll-like receptor 3 play a biological role in virus infections?	the toll-like receptor (tlr) family functions to recognize conserved microbial and viral structures with the purpose of activating signal pathways to instigate immune responses against infections by these organisms. for example, in vitro studies reveal that the tlr3 ligand is a double-stranded rna (dsrna), a product of viral infections. from this observation, it has been proposed that tlr3 is likely an important first signal for virus infections. we approached this issue by investigating the rol ...	2004	15110521
loading of mhc class i and ii presentation pathways by exogenous antigens: a quantitative in vivo comparison.	the mhc class i pathway is usually fueled by endogenous ags, while exogenous ags reach the mhc class ii pathway. although exogenous epitopes may also enter the mhc class i pathway, quantification of the efficiency of the process has remained a difficult task. in an attempt of such a quantification, we directly compared the amount of exogenous virus-like particles required for induction of cytotoxic t cell responses by cross-priming with the amount of virus-like particles required for induction o ...	2004	15128799
visualizing the viral burden: phenotypic and functional alterations of t cells and apcs during persistent infection.	persistent viral infections continue to present major public health problems. failure to achieve virus control confronts the immune system with a chronic viral burden that may involve immune cells themselves and directly compromise the functionality of effector lymphocytes and apcs. in this study we use the lymphocytic choriomeningitis virus system for persistent viral infection of its natural murine host and use analytical techniques for direct ex vivo visualization of virus-infected immune cel ...	2004	15128812
viral flip impairs survival of activated t cells and generation of cd8+ t cell memory.	viral flips (vflips) interfere with apoptosis signaling by death-domain-containing receptors in the tnfr superfamily (death receptors). in this study, we show that t cell-specific transgenic expression of mc159-vflip from the human molluscum contagiosum virus blocks cd95-induced apoptosis in thymocytes and peripheral t cells, but also impairs postactivation survival of in vitro activated primary t cells despite normal early activation parameters. mc159 vflip impairs t cell development to a lesse ...	2004	15128821
efficient t-cell surveillance of the cns requires expression of the cxc chemokine receptor 3.	t-cells play an important role in controlling viral infections inside the cns. to study the role of the chemokine receptor cxcr3 in the migration and positioning of virus-specific effector t-cells within the brain, cxcr3-deficient mice were infected intracerebrally with lymphocytic choriomeningitis virus (lcmv). analysis of the induction phase of the antiviral cd8+ t-cell response did not reveal any immune defects in cxcr3-deficient mice. yet, when mice were challenged with lcmv intracerebrally, ...	2004	15152045
cytokine production by virus-specific cd8(+) t cells varies with activation state and localization, but not with tcr avidity.	the ability of virus-specific cd8(+) t cells to produce cytokines was studied in mice infected with lymphocytic choriomeningitis virus and vesicular stomatitis virus. intracellular staining was used to visualize cytokine-producing cd8(+) and cd4(+) t cells. overall, virus-specific cd8(+) t cells produce a similar range of cytokines (ifn-gamma, tnf-alpha, il-2, gm-csf, rantes, mip-1alpha and mip-1beta) as cd4(+) t cells, but the relative distribution of cytokine-producing subsets is different. mo ...	2004	15166455
anti-cd137 antibodies in the treatment of autoimmune disease and cancer.	cd137 (4-1bb), is an inducible t-cell costimulatory receptor and a member of the tumor necrosis factor receptor (tnfr) superfamily. it is expressed on activated t cells and activated natural killer (nk) cells, but is constitutively expressed on a population of splenic dendritic cells (dcs). the natural counter receptor for cd137 is 4-1bb ligand, a member of the tnf superfamily that is weakly expressed on naïve or resting b cells, macrophages, and dcs. upon activation, the level of 4-1bbl express ...	2004	15181282
role of cell cycle regulator e2f1 in regulating cd8 t cell responses during acute and chronic viral infection.	to determine the role of cell cycle regulatory protein e2f1 in t cell immunity, we compared antigen-specific cd8 t cell responses between wild type (+/+) and e2f1-deficient (e2f1-/-) mice following an acute and chronic infection with lymphocytic choriomeningitis virus (lcmv). during an acute lcmv infection, although lcmv-specific effector cd8 t cells from e2f1-/- mice were less susceptible to activation-induced cell death (aicd) in vitro, e2f1 deficiency had no significant effect on the: (1) exp ...	2004	15207641
origin and fate of lymphocytic choriomeningitis virus-specific cd8+ t cells coexpressing the inhibitory nk cell receptor ly49g2.	cd8+ t cells that coexpress the inhibitory nk cell receptor, ly49g2 (g2), are present in immunologically naive c57bl/6 mice but display ags found on memory t cells. to assess how g2+cd8+ cells relate to bona fide memory cells, we examined the origin and fate of lymphocytic choriomeningitis virus (lcmv)-induced g2+cd8+ cells. during early (day 4) acute lcmv infection, both g2+ and g2-cd8+ t cell subsets underwent an attrition in number and displayed an activation (cd69(high)1b11(high)cd62l(low)) ...	2004	15210808
lentiviral transduction of dendritic cells confers protective antiviral immunity in vivo.	control of a viral infection in vivo requires a rapid and efficient cytotoxic-t-lymphocyte response. we demonstrate that lentivirus-mediated introduction of antigen in dendritic cells confers a protective antiviral immunity in vivo in a lymphocytic choriomeningitis virus model. therefore, lentiviral vectors may be excellent vaccine candidates for viral infections.	2004	15220461
peptide variants of viral ctl epitopes mediate positive selection and emigration of ag-specific thymocytes in vivo.	during development, thymocytes carrying tcrs mediating low-affinity interactions with mhc-bound self-peptides are positively selected for export into the mature peripheral t lymphocyte pool. thus, exogenous administration of certain altered peptide ligands (apl) with reduced tcr affinity relative to cognate ags may provide a tool to elicit maturation of desired tcr specificities. to test this "thymic vaccination" concept, we designed apl of the viral ctl epitopes gp33-41 and vesicular stomatitis ...	2004	15240703
electron microscopy of an alpha-dystroglycan fragment containing receptor sites for lymphocytic choriomeningitis virus and laminin, and use of the receptoid body as a reagent to neutralize virus.	we report the electron microscopic structure of an alpha-dystroglycan (alpha-dg) fragment (dgekfc4) that contains binding sites for lymphocytic choriomeningitis virus (lcmv) and the extracellular matrix (ecm) molecule laminin. in electron microscopic images, dgekfc4 appears as dumbbell-shaped rods with a length of 7.5 +/- 0.5 nm and width of 3 +/- 0.3 nm. the c-terminal human fc allows binding of anti-human fc antibody resulting in formation of immune complexes that preserve alpha-dg binding to ...	2004	15246261
use of alternative receptors different than alpha-dystroglycan by selected isolates of lymphocytic choriomeningitis virus.	long-term infections with viruses permit the generation of variants that evolve specific growth advantages in certain tissues and may show altered disease potentials. the selection of such variants is influenced by the host tissue and often involves virus-receptor interactions. here we report studies of receptor usage by several lymphocytic choriomeningitis virus (lcmv) isolates that expressed different disease patterns. consistent with our previous studies, we found that, with one exception, mu ...	2004	15246281
urolithiasis associated with experimental lymphocytic choriomeningitis virus inoculation in lewis rats.	a high frequency of struvite urolithiasis, hydronephrosis, and other urinary tract lesions developed in a group of lewis rats inoculated intracranially with lymphocytic choriomeningitis virus (lcmv). initially, clinically ill rats were referred to necropsy: 30 rats over 3 years. these rats had high frequency of urolithiasis (8/30, 27%), hydronephrosis (12/30, 40%), cystitis (9/30, 30%), transitional cell carcinoma (4/30, 13%), and pyelonephritis (19/30, 63%). lesions were more common in lcmv-ino ...	2004	15253279
neutrophil involvement in cross-priming cd8+ t cell responses to bacterial antigens.	substantial cd8(+) t cell responses are generated after infection of mice with recombinant listeria monocytogenes strains expressing a model epitope (lymphocytic choriomeningitis virus np(118-126)) in secreted and nonsecreted forms. l. monocytogenes gains access to the cytosol of infected cells, where secreted ags can be accessed by the endogenous mhc class i presentation pathway. however, the route of presentation of the nonsecreted ag in vivo remains undefined. in this study we show that neutr ...	2004	15265934
cutting edge: distinct roles for t help and cd40/cd40 ligand in regulating differentiation of proliferation-competent memory cd8+ t cells.	murine primary antiviral cytotoxic t cell (ctl) responses are often induced in the absence of th cells. in this study, we show that virus-like particles, if combined with dna rich in cpg motifs, efficiently trigger primary ctl responses and comparable frequencies of memory ctls in the presence or absence of t help. however, memory ctls primed in the absence of t help failed to proliferate upon viral challenge. nevertheless, they were efficiently recruited to sites of inflammation, indicating tha ...	2004	15294930
functional characterization of mhc class ii-restricted cd8+cd4- and cd8-cd4- t cell responses to infection in cd4-/- mice.	classical cd4(+) and cd8(+) t cells recognize ag presented by mhc class ii (mhcii) and mhc class i (mhci), respectively. however, our results show that cd4(-/-) mice mount a strong, readily detectable cd8(+) t cell response to mhcii-restricted epitopes after a primary bacterial or viral infection. these mhcii-restricted cd8(+)cd4(-) t cells are more similar to classical cd8(+) t cells than to cd4(+) t cells in their expression of effector functions during a primary infection, yet they also diffe ...	2004	15294964
partial activation of neonatal cd11c+ dendritic cells and induction of adult-like cd8+ cytotoxic t cell responses by synthetic microspheres.	neonatal cytotoxic t cell responses have only been elicited to date with immunogens or delivery systems inducing potent direct apc activation. to define the minimal activation requirements for the induction of neonatal cd8(+) cytotoxic responses, we used synthetic microspheres (ms) coated with a single cd8(+) t cell peptide from lymphocytic choriomeningitis virus (lcmv) or hiv-1. unexpectedly, a single injection of peptide-conjugated ms without added adjuvant induced cd4-dependent ag-specific ne ...	2004	15294984
oral administration with papillomavirus pseudovirus encoding il-2 fully restores mucosal and systemic immune responses to vaccinations in aged mice.	infectious diseases are one of the major threats for the elderly because their immune system is often compromised, and vaccinations to prevent these infections are not effective. a major defect in their immune system seems to be the inability of t cells to produce il-2. we used papillomavirus (pv) pseudoviruses (psvs) as a model vaccine and a gene delivery vector to address how to enhance immune responses to vaccinations. we found that oral immunization with pv psv induced minimal mucosal and sy ...	2004	15294987
deliberate removal of t cell help improves virus-neutralizing antibody production.	the b cell response to lymphocytic choriomeningitis virus is characterized by a cd4(+) t cell-dependent polyclonal hypergammaglobulinemia and delayed formation of virus-specific neutralizing antibodies. here we provide evidence that, paradoxically, because of polyclonal b cell activation, virus-specific t cell help impairs the induction of neutralizing antibody responses. experimental reduction in cd4(+) t cell help in vivo resulted in potent neutralizing antibody responses without impairment of ...	2004	15300247
cd4+ t cells are required for the maintenance, not programming, of memory cd8+ t cells after acute infection.	immunization in the absence of cd4(+) t cell help results in defective cd8(+) t cell memory, deficient recall responses and diminished protective immunity. here we investigated at what stage during the immune response to pathogen cd4(+) t cells are essential in the promotion of functional cd8(+) t cell memory. memory cd8(+) t cell numbers decreased gradually in the absence of cd4(+) t cells despite the presence of similar numbers of memory cell precursors at the peak of the effector phase. adopt ...	2004	15300249
altered cd45 isoform expression affects lymphocyte function in cd45 tg mice.	transgenic mice have been constructed expressing high (cd45rabc) and low (cd45r0) molecular weight cd45 isoforms on a cd45-/- background. phenotypic analysis and in vivo challenge of these mice with influenza and lymphocytic choriomeningitis viruses shows that t cell differentiation and peripheral t cell function are related to the level of cd45 expression but not to which cd45 isoform is expressed. in contrast, b cell differentiation is not restored, irrespective of the level of expression of a ...	2004	15302847
regulation of innate and adaptive immune responses by map kinase phosphatase 5.	mitogen-activated protein (map) kinases are essential regulators in immune responses, and their activities are modulated by kinases and phosphatases. map kinase phosphatase (mkp) is a family of dual-specificity phosphatases whose function is evolutionarily conserved. a number of mammalian mkps have been identified so far, but their specific physiological functions in negative regulation of map kinases have not been genetically defined. here we examine innate and adaptive immune responses in the ...	2004	15306813
serine protease inhibitor 2a is a protective factor for memory t cell development.	an essential event in the development of memory cd8(+) t lymphocytes is the escape of progenitors from programmed cell death, but how this is mediated is unclear. here we report that the gene encoding serine protease inhibitor 2a (spi2a), an inhibitor of lysosomal executioner proteases dependent on transcription factor nf-kappab, is upregulated in memory cell precursors. spi2a upregulation protected lymphocytic choriomeningitis virus-specific memory progenitors from programmed cell death. thus, ...	2004	15311278
constitutive expression of ccr7 directs effector cd8 t cells into the splenic white pulp and impairs functional activity.	antigenic stimulation down-regulates ccr7 on effector t cells. to analyze the importance of ccr7 down-regulation, transgenic (tg) mice constitutively expressing ccr7 were generated. cd8 t cells with defined ag specificity were obtained by breeding ccr7-tg mice with p14 tcr-tg mice specific for lymphocytic choriomeningitis virus. transgenic ccr7 expression did not impair proliferation of p14.ccr7 t cells induced by lymphocytic choriomeningitis virus infection, but prevented ccr7 down-regulation. ...	2004	15322160
lcmv-mediated hepatitis in rhesus macaques: we but not arm strain activates hepatocytes and induces liver regeneration.	lymphocytic chorimeningitis virus (lcmv), the prototype arenavirus, and lassa virus (lasv), causative agent of lassa hemorrhagic fever (lhf), belong to the old world group of the family arenaviridae. both viruses have extensive strain diversity and significant variations in lethality and pathogenicity for man and experimental animals. we have shown that the lhf-like infection of rhesus macaques with the we strain of lcmv affects liver functions, induces hepatocyte proliferation, and causes a ris ...	2004	15338320
molecular characterization of virus-induced autoantibody responses.	here we present a comprehensive molecular mapping of virus-induced autoimmune b cell responses obtained by serological identification of antigens by recombinant expression cloning analysis. immunoscreening of cdna expression libraries of various organs (lung, liver, and spleen) using sera from mice infected with cytopathic (vaccinia virus [vv]) or noncytopathic (lymphocytic choriomeningitis virus [lcmv]) viruses revealed a broad specificity of the elicited autoantibody response. interestingly, t ...	2004	15353556
a role for the granzyme b inhibitor serine protease inhibitor 6 in cd8+ memory cell homeostasis.	generation and maintenance of protective immunological memory is the goal of vaccination programs. it has recently become clear that cd8+ memory t cells are derived directly from ctls. the mechanisms underlying this transformation and the subsequent survival of memory cells are not completely understood. however, some effector molecules required by ctls to eliminate infected cells have also been shown to control the number of ag-specific cells. we report that memory cells express high levels of ...	2004	15356127
cd8 t cell responses to lymphocytic choriomeningitis virus in early growth response gene 1-deficient mice.	previous in vitro work has implicated a role for transcriptional factor early growth response gene 1 (egr1) in regulating immune responses. however, the in vivo role of egr1 in orchestrating t cell responses has not been studied. to investigate the importance of egr1 in t cell immunity, we compared ag-specific cd8 t cell responses between wild type (+/+) and egr1-deficient (egr1-/-) mice following an acute infection with lymphocytic choriomeningitis virus (lcmv). these studies revealed that the ...	2004	15356133
immunoproteasomes down-regulate presentation of a subdominant t cell epitope from lymphocytic choriomeningitis virus.	the cytotoxic t cell response to pathogens is usually directed against a few immunodominant epitopes, while other potential epitopes are either subdominant or not used at all. in c57bl/6 mice, the acute cytotoxic t cell response against lymphocytic choriomeningitis virus is directed against immunodominant epitopes derived from the glycoprotein (gp33-41) and the nucleoprotein (np396-404), while the gp276-286 epitope remains subdominant. despite extensive investigations, the reason for this hierar ...	2004	15356141
public, private and non-specific antibodies induced by non-cytopathic viral infections.	lymphocytic choriomeningitis virus (lcmv) represents a useful experimental model of murine infection with a non-cytopathic virus, bearing resemblance to hiv and hepatitis c virus (hcv) infections in humans. recent data from the lcmv model indicate that the humoral immune response that is induced by non-cytopathic viruses is far more complex than previously appreciated. lcmv-induced igg production is largely polyclonal, with more than 90% of the antibody repertoire constituting non-relevant speci ...	2004	15358263