Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
|---|
| analysis of direct and cross-presentation of antigens in tppii knockout mice. | tripeptidyl peptidase ii (tppii) is an oligopeptidase forming giant complexes in the cytosol that have high exo-, but also, endoproteolytic activity. immunohistochemically, the complexes appear as distinct foci in the cytosol. in part controversial biochemical and functional studies have suggested that tppii contributes, on the one hand, positively to ag processing by generating epitope carboxyl termini or by trimming epitope precursors, and, on the other, negatively by destroying potentially an ... | 2007 | 18056356 |
| tnf-alpha is critical for antitumor but not antiviral t cell immunity in mice. | tnf-alpha antagonists are widely used in the treatment of inflammatory and autoimmune diseases, but their use is associated with reactivation of latent infections. this highlights the importance of tnf-alpha in immunity to certain pathogens and raises concerns that critical aspects of immune function are impaired in its absence. unfortunately, the role of tnf-alpha in the regulation of t cell responses is clouded by a myriad of contradictory reports. here, we show a role for tnf-alpha and its re ... | 2007 | 17992258 |
| "negative vaccination" by specific cd4 t cell tolerisation enhances virus-specific protective antibody responses. | cooperation of cd4+ t helper cells with specific b cells is crucial for protective vaccination against pathogens by inducing long-lived neutralizing antibody responses. during infection with persistence-prone viruses, prolonged virus replication correlates with low neutralizing antibody responses. we recently described that a viral mutant of lymphocytic choriomeningitis virus (lcmv), which lacks a t helper epitope, counterintuitively induced an enhanced protective antibody response. likewise, pa ... | 2007 | 18000535 |
| normal brain cells contribute to the bystander effect in suicide gene therapy of malignant glioma. | lentiviral vectors pseudotyped with glycoproteins of the lymphocytic choriomeningitis virus (lcmv-gp) are promising candidates for gene therapy of malignant glioma, as they specifically and efficiently transduce glioma cells in vitro and in vivo. here, we evaluated the therapeutic efficacy of lcmv-gp and vesicular stomatitis virus glycoprotein (vsv-g) pseudotyped vectors. | 2007 | 18006778 |
| molecular signature of cd8+ t cell exhaustion during chronic viral infection. | chronic viral infections often result in t cell exhaustion. to determine the molecular signature of exhaustion, we compared the gene-expression profiles of dysfunctional lymphocytic choriomeningitis virus (lcmv)-specific cd8(+) t cells from chronic infection to functional lcmv-specific effector and memory cd8(+) t cells generated after acute infection. these data showed that exhausted cd8(+) t cells: (1) overexpressed several inhibitory receptors, including pd-1, (2) had major changes in t cell ... | 2007 | 17950003 |
| defective t helper response of hepatocyte-stimulated cd4 t cells impairs antiviral cd8 response and viral clearance. | in hepatitis, hepatocytes gain the ability to express major histocompatibility complex (mhc) class ii molecules and to present antigen to cd4 t cells. here, we investigated whether mhc class ii-expressing hepatocytes influence in vitro the differentiation of cd4 t cells and in vivo the t-cell response to and control of viral infection. | 2007 | 17967458 |
| type i interferon during viral infections: multiple triggers for a multifunctional mediator. | type i interferons (ifn-i) orchestrate numerous biological and cellular processes and are essential elements during host antiviral defense. after recognition of highly conserved virus signatures, a complex network of signaling events is rapidly initiated and leads to ifn-i synthesis. these cytokines directly induce a strong antiviral state and exert several immune-regulatory actions aimed at preventing virus spread. on the other hand, viruses evolved to evade or subvert the ifn-i system for thei ... | 2007 | 17969455 |
| strength of stimulus and clonal competition impact the rate of memory cd8 t cell differentiation. | the developmental pathways of long-lived memory cd8 t cells and the lineage relationship between memory t cell subsets remain controversial. although some studies indicate the two major memory t cell subsets, central memory t (t(cm)) and effector memory t (t(em)), are related lineages, others suggest that these subsets arise and are maintained independently of one another. in this study, we have investigated this issue and examined the differentiation of memory cd8 t cell subsets by tracking the ... | 2007 | 17982060 |
| extralymphatic virus sanctuaries as a consequence of potent t-cell activation. | t helper cells can support the functions of cd8(+) t cells against persistently infecting viruses such as murine lymphocytic choriomeningitis virus (lcmv), cytomegalovirus, hepatitis c virus and hiv. these viruses often resist complete elimination and remain detectable at sanctuary sites, such as the kidneys and other extralymphatic organs. the mechanisms underlying this persistence are not well understood. here we show that mice with potent virus-specific t-cell responses have reduced levels an ... | 2007 | 17982463 |
| old world arenavirus infection interferes with the expression of functional alpha-dystroglycan in the host cell. | alpha-dystroglycan (alpha-dg) is an important cellular receptor for extracellular matrix (ecm) proteins as well as the old world arenaviruses lymphocytic choriomeningitis virus (lcmv) and the human pathogenic lassa fever virus (lfv). specific o-glycosylation of alpha-dg is critical for its function as receptor for ecm proteins and arenaviruses. here, we investigated the impact of arenavirus infection on alpha-dg expression. infection with an immunosuppressive lcmv isolate caused a marked reducti ... | 2007 | 17761532 |
| programmed death-1 (pd-1) defines a transient and dysfunctional oligoclonal t cell population in acute homeostatic proliferation. | the host responds to lymphopenic environments by acute homeostatic proliferation, which is a cytokine- and endogenous peptide-driven expansion of lymphocytes that restores the numbers and diversity of t cells. it is unknown how these homeostatically proliferating (hp) cells are ultimately controlled. using a system where lymphocytic choriomeningitis virus-immune c57bl/6 splenocytes were transferred into lymphopenic t cell-deficient hosts and allowed to reconstitute the environment, we defined th ... | 2007 | 17785507 |
| differential inhibition of type i interferon induction by arenavirus nucleoproteins. | we have documented that the nucleoprotein (np) of the prototypic arenavirus lymphocytic choriomeningitis virus is an antagonist of the type i interferon response. in this study we tested the ability of nps encoded by representative arenavirus species from both old world and new world antigenic groups to inhibit production of interferon. we found that, with the exception of tacaribe virus (tcrv), all nps tested inhibited activation of beta interferon and interferon regulatory factor 3 (irf-3)-dep ... | 2007 | 17804508 |
| signal peptide requirements for lymphocytic choriomeningitis virus glycoprotein c maturation and virus infectivity. | insertion of the lymphocytic choriomeningitis virus (lcmv) precursor glycoprotein c (gp-c) into the membrane of the endoplasmic reticulum is mediated by an unusual signal peptide (sp(gp-c)). it is comprised of 58 amino acid residues and contains an extended hydrophilic n-terminal region, two hydrophobic regions, and a short c-terminal region. after cleavage by signal peptidase, sp(gp-c) accumulates in cells and virus particles. in the present study, we identified the lcmv sp(gp-c) as being an es ... | 2007 | 17804515 |
| high basal stat4 balanced by stat1 induction to control type 1 interferon effects in natural killer cells. | the best-characterized type 1 interferon (ifn) signaling pathway depends on signal transducer and activator of transcription 1 (stat1) and stat2. the cytokines can, however, conditionally activate all stats. regulation of their access to particular signaling pathways is poorly understood. stat4 is important for ifn-gamma induction, and nk cells are major producers of this cytokine. we report that nk cells have high basal stat4 levels and sensitivity to type 1 ifn-mediated stat4 activation for if ... | 2007 | 17846149 |
| capture of membrane components via trogocytosis occurs in vivo during both dendritic cells and target cells encounter by cd8(+) t cells. | cytotoxic t lymphocytes recently stimulated by antigen-presenting cells (apc) display major histocompatibility class (mhc) i and ii molecules inherited from apc. we have previously reported that, in vitro, transfer of mhc molecules and several other proteins occurs through trogocytosis, i.e. the active acquisition of target cell membrane fragments by t lymphocytes. here, using the model of viral antigen lcmvgp33-41 recognition in transgenic p14 mice, we show that cd8(+) t cells perform trogocyto ... | 2007 | 17850589 |
| immune suppression or enhancement by cd137 t cell costimulation during acute viral infection is time dependent. | cd137 is expressed on activated t cells and ligands to this costimulatory molecule have clinical potential for amplifying cd8 t cell immunity to tumors and viruses, while suppressing cd4 autoimmune t cell responses. to understand the basis for this dichotomy in t cell function, cd4 and cd8 antiviral immunity was measured in lymphocytic choriomeningitis virus (lcmv) armstrong- or a/pr8/34 influenza-infected mice injected with anti-cd137 mabs. we found that the timing of administration of anti-cd1 ... | 2007 | 17853940 |
| superinfection exclusion in bhk-21 cells persistently infected with junín virus. | we characterized a persistently junín virus (junv)-infected bhk-21 cell line obtained by experimental infection with the xjcl3 strain. this cell line, named k3, produced low levels of virus in supernatants which were not influenced by the presence of defective interfering (di) particles after the first year of infection. k3 cells were able to exclude superinfection of the homologous junv and the antigenically related tacaribe virus (tcrv), whereas the non-related arenaviruses lymphocytic choriom ... | 2007 | 17872526 |
| viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection. | many chronic viral infections are marked by pathogen persistence and a generalized immunosuppression. the exact mechanisms by which this occurs are still unknown. using a mouse model of persistent lymphocytic choriomeningitis virus (lcmv) infection, we demonstrate viral targeting of fibroblastic reticular cells (frc) in the lymphoid organs. the frc stromal networks are critical for proper lymphoid architecture and function. high numbers of frc were infected by lcmv clone 13, which causes a chron ... | 2007 | 17878315 |
| normal establishment of virus-specific memory cd8 t cell pool following primary infection during pregnancy. | suppression of cell-mediated immunity has been proposed as a mechanism that promotes maternal tolerance of the fetus but also contributes to increased occurrence and severity of certain infections during pregnancy. despite decades of research examining the effect of pregnancy on ag-specific t cell responses, many questions remain. in particular, quantitative examination of memory cd8 t cell generation following infection during pregnancy remains largely unknown. to examine this issue, we evaluat ... | 2007 | 17878333 |
| differential effect of listeria monocytogenes infection on cytokine production and cytotoxicity of cd8 t cells. | bacterial infection induces a shift to type 1 cd4 t cell subset in an infected host and this shift is important for protection of the host from disease development. many researchers think that the shift is antigen-dependent, but we previously demonstrated an initial induction step for cd4 t cell subsets during listeria monocytogenes (lm) infection is antigen-independent. although listeria is a tlr2 ligand, the immune system of the lm-infected host responded to the pathogen to induce expression o ... | 2007 | 17895607 |
| rt-pcr assay for detection of lassa virus and related old world arenaviruses targeting the l gene. | this study describes an rt-pcr assay targeting the l rna segment of arenaviruses. conserved regions were identified in the polymerase domain of the l gene on the basis of published sequences for lassa virus, lymphocytic choriomeningitis virus (lcmv), pichinde virus and tacaribe virus, as well as 15 novel sequences for lassa virus, lcmv, ippy virus, mobala virus and mopeia virus determined in this study. using these regions as target sites, a pcr assay for detection of all known old world arenavi ... | 2007 | 17905372 |
| discriminating between different pathways of memory cd8+ t cell differentiation. | despite the rapid accumulation of quantitative data on the dynamics of cd8(+) t cell responses following acute viral or bacterial infections of mice, the pathways of differentiation of naive cd8(+) t cells into memory during an immune response remain controversial. currently, three models have been proposed. in the "stem cell-associated differentiation" model, following activation, naive t cells differentiate into stem cell-like memory cells, which then convert into terminally differentiated sho ... | 2007 | 17911585 |
| abrogation of ccl21 chemokine function by transgenic over-expression impairs t cell immunity to local infections. | the cc chemokine receptor 7 (ccr7) and its two ligands, ccl21 and ccl19, play an important role in migration of immune cells to lymphoid tissue. to analyze the function of ccr7 in t cell immunity to infectious agents in vivo, transgenic (tg) mice expressing ccl21 in an ubiquitous fashion were generated. these mice contained high amounts of ccl21 in the serum ( approximately 0.3 microg/ml that resulted in ccr7 down-regulation and in a strongly impaired migration of t cells toward ccl21 in vitro. ... | 2007 | 17914120 |
| coordinated regulation and widespread cellular expression of interferon-stimulated genes (isg) isg-49, isg-54, and isg-56 in the central nervous system after infection with distinct viruses. | the interferon (ifn)-stimulated genes (isgs) isg-49, isg-54, and isg-56 are highly responsive to viral infection, yet the regulation and function of these genes in vivo are unknown. we examined the simultaneous regulation of these isgs in the brains of mice during infection with either lymphocytic choriomeningitis virus (lcmv) or west nile virus (wnv). expression of the isg-49 and isg-56 genes increased significantly during lcmv infection, being widespread and localized predominantly to common a ... | 2007 | 17079283 |
| protection against vaccinia virus challenge by cd8 memory t cells resolved by molecular mimicry. | live vaccinia virus (vv) vaccination has been highly successful in eradicating smallpox. however, the mechanisms of immunity involved in mediating this protective effect are still poorly understood, and the roles of cd8 t-cell responses in primary and secondary vv infections are not clearly identified. by applying the concept of molecular mimicry to identify potential cd8 t-cell epitopes that stimulate cross-reactive t cells specific to lymphocytic choriomeningitis virus (lcmv) and vv, we identi ... | 2007 | 17079318 |
| structural and mechanistic features of protein o glycosylation linked to cd8+ t-cell apoptosis. | cd8+ t-cell apoptosis is essential for the contraction phase of the immune response, yet the initiating signals and precise pathways involved are unresolved. the st3gal-i sialyltransferase is a candidate mechanistic component and catalyzes sialic acid addition to core 1 o-glycans during protein o glycosylation. st3gal-i inactivation or enzymatic removal of its product renders cd8+ t cells, but not cd4+ t cells, susceptible to apoptosis by differential cross-linking of o-glycoproteins in the abse ... | 2007 | 17101770 |
| stage of primary infection with lymphocytic choriomeningitis virus determines predisposition or resistance of mice to secondary bacterial infections. | we investigated the effect of a primary non-lethal infection with lymphocytic choriomeningitis virus (lcmv) on the course and outcome of a secondary infection with the gram-negative salmonella enterica serovar typhimurium or the gram-positive listeria monocytogenes in mice. we found that at each stage of the viral infection the susceptibility of mice to bacterial super-infections changes dramatically and depends also on whether the secondary infection is a gram-positive or gram-negative one. the ... | 2007 | 17136407 |
| quantitating the magnitude of the lymphocytic choriomeningitis virus-specific cd8 t-cell response: it is even bigger than we thought. | measuring the magnitudes and specificities of antiviral cd8 t-cell responses is critical for understanding the dynamics and regulation of adaptive immunity. despite many excellent studies, the accurate measurement of the total cd8 t-cell response directed against a particular infection has been hampered by an incomplete knowledge of all cd8 t-cell epitopes and also by potential contributions of bystander expansion among cd8 t cells of irrelevant specificities. here, we use several techniques to ... | 2007 | 17151096 |
| dynamics and magnitude of virus-induced polyclonal b cell activation mediated by bcr-independent presentation of viral antigen. | hypergammaglobulinemia and production of autoantibodies occur during many viral infections, and studies have suggested that viral antigen-presenting b cells may become polyclonally activated by cd4 t cells in vivo in the absence of viral engagement of the bcr. however, we have reported that cd4 cells in lymphocytic choriomengitis virus (lcmv)-infected mice kill adoptively transferred b cells coated with lcmv class ii peptides. we report here that most of the surviving naïve b cells presenting cl ... | 2007 | 17163452 |
| hla-a2-restricted protection against lethal lymphocytic choriomeningitis. | the consequences of human lymphocytic choriomeningitis virus (lcmv) infection can be severe, including aseptic meningitis in immunocompetent individuals, hydrocephalus or chorioretinitis in fetal infection, or a highly lethal outcome in immunosuppressed individuals. in murine models of lcmv infection, cd8(+) t cells play a primary role in providing protective immunity, and there is evidence that cellular immunity may also be important in related arenavirus infections in humans. for this reason, ... | 2007 | 17166907 |
| virally activated cd8 t cells home to mycobacterium bovis bcg-induced granulomas but enhance antimycobacterial protection only in immunodeficient mice. | the effect of secondary infections on cd4 t-cell-regulated chronic granulomatous inflammation is not well understood. here, we have investigated the effect of an acute viral infection on the cellular composition and bacterial protection in mycobacterium bovis strain bacille calmette-guérin (bcg)-induced granulomas using an immunocompetent and a partially immunodeficient murine model. acute lymphocytic choriomeningitis virus (lcmv) coinfection of c57bl/6 mice led to substantial accumulation of ga ... | 2007 | 17178783 |
| a-to-g hypermutation in the genome of lymphocytic choriomeningitis virus. | the interferon-inducible adenosine deaminase that acts on double-stranded rna (adar1-l) has been proposed to be one of the antiviral effector proteins within the complex innate immune response. here, the potential role of adar1-l in the innate immune response to lymphocytic choriomeningitis virus (lcmv), a widely used virus model, was studied. infection with lcmv clearly upregulated adar1-l expression and activity. the editing activity of adar1-l on an rna substrate was not inhibited by lcmv rep ... | 2007 | 17020943 |
| induction and maintenance of cd8+ t cells specific for persistent viruses. | 2007 | 17191382 | |
| sap regulation of follicular helper cd4 t cell development and humoral immunity is independent of slam and fyn kinase. | mutations in sh2d1a resulting in lack of slam-associated protein (sap) expression cause the human genetic immunodeficiency x-linked lymphoproliferative disease. a severe block in germinal center development and lack of long-term humoral immunity is one of the most prominent phenotypes of sap(-) mice. we show, in this study, that the germinal center block is due to an essential requirement for sap expression in ag-specific cd4 t cells to develop appropriate follicular helper t cell functions. it ... | 2007 | 17202343 |
| prevalence of antibodies to lymphocytic choriomeningitis virus in blood donors in southeastern france. | 2007 | 17207247 | |
| pivotal advance: ctla-4+ t cells exhibit normal antiviral functions during acute viral infection. | previous studies have shown that t cells, which are genetically deficient in ctla-4/cd152 expression, will proliferate uncontrollably, resulting in lethal autoimmune disease. this and other evidence indicate that ctla-4 plays a critical role in the negative regulation of effector t cell function. in contrast to expectations, brdu incorporation experiments demonstrated that ctla-4 expression was associated with normal or even enhanced in vivo proliferation of virus-specific cd4+ and cd8+ t cells ... | 2007 | 17215523 |
| ifn-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and sindbis viruses. | type i interferons (ifns) play an essential role in the host response to viral infection through the induction of numerous ifn-stimulated genes (isgs), including important antiviral molecules such as pkr, rnase l, mx, and inos. yet, additional antiviral isgs likely exist. ifn-stimulated gene 15 (isg15) is a ubiquitin homolog that is rapidly up-regulated after viral infection, and it conjugates to a wide array of host proteins. although it has been hypothesized that isg15 functions as an antivira ... | 2007 | 17227866 |
| agonistic anti-cd40 antibody profoundly suppresses the immune response to infection with lymphocytic choriomeningitis virus. | previous work has shown that agonistic abs to cd40 (anti-cd40) can boost weak cd8 t cell responses as well as substitute for cd4 t cell function during chronic gammaherpes virus infection. agonistic anti-cd40 treatment has, therefore, been suggested as a potential therapeutic strategy in immunocompromised patients. in this study, we investigated whether agonistic anti-cd40 could substitute for cd4 t cell help in generating a sustained cd8 t cell response and prevent viral recrudescence following ... | 2007 | 17237416 |
| contributions of the lymphocytic choriomeningitis virus glycoprotein and polymerase to strain-specific differences in murine liver pathogenicity. | hepatic involvement is commonly observed in arenavirus infections, but the viral determinants of liver disease are only partially understood. here we exploited newly developed reverse-genetic techniques with lymphocytic choriomeningitis virus (lcmv), the prototype arenavirus, to address specifically the contribution of the viral glycoprotein (gp) to liver pathogenicity. it is well established that strain we, but not arm, causes hepatitis in mice. we found that this property correlated with the s ... | 2007 | 17251578 |
| immunization with non-replicating e. coli minicells delivering both protein antigen and dna protects mice from lethal challenge with lymphocytic choriomeningitis virus. | in the midst of new investigations into the mechanisms of both delivery and protection of new vaccines and vaccine carriers, it has become clear that immunization with delivery mechanisms that do not involve living, replicating organisms are vastly preferred. in this report, non-replicating bacterial minicells simultaneously co-delivering the nucleoprotein (np) of lymphocytic choriomeningitis virus (lcmv) and the corresponding dna vaccine were tested for the ability to generate protective cellul ... | 2007 | 17258845 |
| gene transfer in human skin with different pseudotyped hiv-based vectors. | pseudotyping lentiviral vector with other viral surface proteins could be applied for treating genetic anomalies in human skin. in this study, the modification of hiv vector tropism by pseudotyping with the envelope glycoprotein from vesicular stomatitis virus (vsv), the zaire ebola (eboz) virus, murine leukemia virus (mulv), lymphocytic choriomeningitis virus (lcmv), rabies or the rabies-related mokola virus encoding lacz as a reporter gene was evaluated qualitatively and quantitatively in huma ... | 2007 | 17268532 |
| the role of endoplasmic reticulum-associated aminopeptidase 1 in immunity to infection and in cross-presentation. | endoplasmic reticulum-associated aminopeptidase 1 (erap1) is involved in the final processing of endogenous peptides presented by mhc class i molecules to ctls. we generated erap1-deficient mice and analyzed cytotoxic responses upon infection with three viruses, including lymphocytic choriomeningitis virus, which causes vigorous t cell activation and is controlled by ctls. despite pronounced effects on the presentation of selected epitopes, the in vivo cytotoxic response was altered for only one ... | 2007 | 17277129 |
| analysis of cd8+ t cell-mediated anti-viral responses in mice with targeted deletions of the m1 or m5 muscarinic cholinergic receptors. | a number of studies have demonstrated that non-neuronal acetylcholine can play a role in the regulation of t cell function. recently, we reported that cd8(+) t cells, from mice with a targeted deletion of the m(1) muscarinic receptor, had a defect in differentiating into cytolytic t lymphocytes when stimulated in vitro. in the current report, we analyze the in vivo function of cd8(+) t cells from mice with targeted deletions of either m(1) or m(5) muscarinic receptors. m(1) or m(5) knockout mice ... | 2007 | 17286988 |
| transferrin receptor 1 is a cellular receptor for new world haemorrhagic fever arenaviruses. | at least five arenaviruses cause viral haemorrhagic fevers in humans. lassa virus, an old world arenavirus, uses the cellular receptor alpha-dystroglycan to infect cells. machupo, guanarito, junin and sabia viruses are new world haemorrhagic fever viruses that do not use alpha-dystroglycan. here we show a specific, high-affinity association between transferrin receptor 1 (tfr1) and the entry glycoprotein (gp) of machupo virus. expression of human tfr1, but not human transferrin receptor 2, in ha ... | 2007 | 17287727 |
| potent t cell agonism mediated by a very rapid tcr/pmhc interaction. | the interaction between t cell receptors (tcr) and peptide-major histocompatibility complex (pmhc) antigens can lead to varying degrees of agonism (t cell activation), or antagonism. the p14 tcr recognises the lymphocytic choriomeningitis virus (lcmv)-derived peptide, gp33 residues 33-41 (kavynfatc), presented in the context of h-2d(b). the cellular responses to various related h-2d(b) peptide ligands are very well characterised, and p14 tcr-transgenic mice have been used extensively in models o ... | 2007 | 17295390 |
| priming of cd8+ t cell responses by pathogens typically depends on cd70-mediated interactions with dendritic cells. | the cd27/cd70-interaction has been shown to provide a costimulatory and survival signal for t cells in vitro and in vivo. recently, cd70 expression by dc was found to be important for the priming of cd8+ t cells. we show here that blocking cd70 interactions has a significant impact on priming of cd8+ t cell responses by vaccinia virus (vv), listeria monocytogenes and vesicular stomatitis virus (vsv) in mice. however, the priming of specific cd8+ t cells upon infection with lymphocytic choriomeni ... | 2007 | 17295392 |
| zoonoses in solid-organ and hematopoietic stem cell transplant recipients. | numerous reports exist of the transmission of zoonoses to humans during and after solid-organ and hematopoietic stem cell transplantation. donor-derived infections of numerous etiologies, including west nile virus infection, chagas disease, toxoplasmosis, rabies, lymphocytic choriomeningitis virus infection, and infection due to brucella species have been reported. most zoonoses occur as a primary infection after transplantation, and immunocompromised patients are more likely to experience signi ... | 2007 | 17304461 |
| mapping and restriction of a dominant viral cd4+ t cell core epitope by both mhc class i and mhc class ii. | virus-specific cd4(+) t cells contribute to effective virus control through a multiplicity of mechanisms including direct effector functions as well as "help" for b cell and cd8(+) t cell responses. here, we have used the lymphocytic choriomeningitis virus (lcmv) system to assess the minimal constraints of a dominant antiviral cd4(+) t cell response. we report that the core epitope derived from the lcmv glycoprotein (gp) is 11 amino acids in length and provides optimal recognition by epitope-spe ... | 2007 | 17320138 |
| process noise: an explanation for the fluctuations in the immune response during acute viral infection. | the parameters of the immune response dynamics are usually estimated by the use of deterministic ordinary differential equations that relate data trends to parameter values. since the physical basis of the response is stochastic, we are investigating the intensity of the data fluctuations resulting from the intrinsic response stochasticity, the so-called process noise. dealing with the cd8+ t-cell responses of virus-infected mice, we find that the process noise influence cannot be neglected and ... | 2007 | 17325020 |
| the cd8+ t-cell response to lymphocytic choriomeningitis virus involves the l antigen: uncovering new tricks for an old virus. | cd8(+) t-cell responses control lymphocytic choriomeningitis virus (lcmv) infection in h-2(b) mice. although antigen-specific responses against lcmv infection are well studied, we found that a significant fraction of the cd8(+) cd44(hi) t-cell response to lcmv in h-2(b) mice was not accounted for by known epitopes. we screened peptides predicted to bind major histocompatibility complex class i and overlapping 15-mer peptides spanning the complete lcmv proteome for gamma interferon (ifn-gamma) in ... | 2007 | 17329346 |
| a role for cd44 in t cell development and function during direct competition between cd44+ and cd44- cells. | the role of cd44 in t cell biology remains incompletely understood. although studies using anti-cd44 antibodies have implicated this cell adhesion molecule in a variety of important t cell processes, few t cell defects have been reported in cd44-deficient mice. we have assessed the requirement for cd44 in t cell development and mature t cell function by analyzing mice in which cd44(-/-) and wt cells were produced simultaneously. in mixed (cd44(-/-) + cd44(+/+)) bone marrow chimeras, production o ... | 2007 | 17330818 |
| il-10, t cell exhaustion and viral persistence. | viral infections can have one of two outcomes: control of viral replication and acute infection or viral persistence and chronic infection. it is clear that both pathogen and host characteristics influence the acute versus chronic outcome of viral infection. the early events in the host immune response that favor immunosuppression and viral persistence, however, have remained poorly understood. using the well-characterized mouse model of acute versus chronic lymphocytic choriomeningitis virus (l ... | 2007 | 17336072 |
| serpin-6 expression protects embryonic stem cells from lysis by antigen-specific ctl. | the immune response to embryonic stem (es) cells is still poorly understood. in this study, we addressed the adaptive cellular immune response to undifferentiated and differentiated es cells infected with lymphocytic choriomeningitis virus (lcmv), a vertically transmitted pathogen in mice and humans. in contrast to the prevailing view, we found that undifferentiated and differentiated murine es cells express mhc class i molecules, although at low levels. when cocultured with lcmv-infected es cel ... | 2007 | 17339433 |
| no essential role for tripeptidyl peptidase ii for the processing of lcmv-derived t cell epitopes. | the proteasome is critically involved in the production of mhc class i-restricted t cell epitopes. approximately 20% of all peptides generated by the proteasome are too large for direct presentation by mhc class i molecules. reits et al. (immunity 2004. 20: 495-506) suggested that a major portion of proteasomal products are larger than 15 amino acids and require further degradation by the tripeptidyl peptidase ii (tppii) before becoming ligands of mhc class i molecules. using the well-characteri ... | 2007 | 17357105 |
| impaired nfat nuclear translocation results in split exhaustion of virus-specific cd8+ t cell functions during chronic viral infection. | in persistent viral infections, the host's immune system is challenged by the constant exposure to antigen, potentially causing continuous activation of cd8(+) t cells with subsequent immunopathology. here we demonstrate, for experimental chronic lymphocytic choriomeningitis virus and human hiv infection, that upon prolonged in vivo exposure to antigen, tcr-triggered ca(2+) flux, degranulation, and cytotoxicity are maintained on a cellular level, whereas cytokine production is severely impaired ... | 2007 | 17360564 |
| old world and clade c new world arenaviruses mimic the molecular mechanism of receptor recognition used by alpha-dystroglycan's host-derived ligands. | alpha-dystroglycan (dg) is an important cellular receptor for extracellular matrix (ecm) proteins and also serves as the receptor for old world arenaviruses lassa fever virus (lfv) and lymphocytic choriomeningitis virus (lcmv) and clade c new world arenaviruses. in the host cell, alpha-dg is subject to a remarkably complex pattern of o glycosylation that is crucial for its interactions with ecm proteins. two of these unusual sugar modifications, protein o mannosylation and glycan modifications i ... | 2007 | 17360738 |
| broad-spectrum antiviral activity of small interfering rna targeting the conserved rna termini of lassa virus. | small interfering rnas targeting the conserved rna termini upstream of np and l gene were found to reduce reporter gene expression from lassa virus replicon and lassa virus mrna expression construct and to inhibit replication of different lassa virus strains, lymphocytic choriomeningitis virus, and mopeia virus in cell culture. | 2007 | 17371814 |
| a suspenseful game of 'hide and seek' between virus and host. | as part of the most important contributions to the understanding of viral immunity, michael oldstone recounts his pioneering work on lymphocytic choriomeningitis virus. | 2007 | 17375090 |
| cytotoxic t cell-mediated diabetes in rip-cd80 transgenic mice: autoantigen peptide sensitivity and fine specificity. | rodent immune-mediated diabetes model studies have advanced understanding of beta cell-specific t cell responses, and the testing of therapeutic approaches. we have used an inducible diabetes model based on rat insulin promotor (rip)-driven expression of cd80 (b7-1) on pancreatic beta cells. using these mice, we have established that immunizing with a single autoantigen can promote progressive islet inflammation and eventually t cell-mediated diabetes. we now describe a potent immunization proto ... | 2007 | 17376836 |
| mapping the landscape of the lymphocytic choriomeningitis virus stable signal peptide reveals novel functional domains. | the stable signal peptide (ssp) of the lymphocytic choriomeningitis virus surface glycoprotein precursor has several unique characteristics. the ssp is unusually long, at 58 amino acids, and contains two hydrophobic domains, and its sequence is highly conserved among both old and new world arenaviruses. to better understand the functions of the ssp, a panel of point and deletion mutants was created by in vitro mutagenesis to target the highly conserved elements within the ssp. we were also able ... | 2007 | 17376927 |
| genetic identification of kodoko virus, a novel arenavirus of the african pigmy mouse (mus nannomys minutoides) in west africa. | genetic evidence of a novel arenavirus species related to but distinct from lymphocytic choriomeningitis virus (lcmv) was obtained from a rodent belonging to an endemic african subgenus of mus (nannomys). the phylogenetic position among old world arenaviruses of this new arenavirus, named kodoko virus, was reconstructed based on l and np genes sequences. the finding of an old world arenavirus related to lcmv outside the known geographical range of lcmv in a novel rodent species reveals new insig ... | 2007 | 17382366 |
| minimal impact of a de novo-expressed beta-cell autoantigen on spontaneous diabetes development in nod mice. | during an autoimmune process, the autoaggressive response spreads from the initiating autoantigen to other antigens expressed in the target organ. based on evidence from experimental models for multiple sclerosis, such "antigenic spreading" can play an important role in the exacerbation of clinical disease. we evaluated whether pathogenesis of spontaneous diabetes in nod mice could be accelerated in a similar way when a novel autoantigen was expressed in pancreatic beta-cells. unexpectedly, we f ... | 2007 | 17395746 |
| indirect regulation of cd4 t-cell responses by tumor necrosis factor receptors in an acute viral infection. | despite the well-recognized importance of cd4 t-cell help in the induction of antibody production and cytotoxic-t-lymphocyte responses, the regulation of cd4 t-cell responses is not well understood. using mice deficient for tnf receptor i (tnfr i) and/or tnfr ii, we show that tnfr i and tnfr ii play redundant roles in down regulating the expansion of cd4 t cells during an acute infection of mice with lymphocytic choriomeningitis virus (lcmv). adoptive transfer experiments using t-cell-receptor t ... | 2007 | 17409152 |
| cure of chronic viral infection by neutralizing antibody treatment. | persistent infections can pose severe health risks. in many cases individuals fail to clear the virus and consequently chronic infection, often associated with severe immunopathology, occurs. for some chronic infections it is known that systemic il-10 production can be increased. however, it is unclear, whether il-10 affects the outcome of infection, amount of immunopathology and could be the actual cause for persistence. conventional interferons (ifn) or anti-viral immunotherapies attempting to ... | 2007 | 17412296 |
| antiviral cd4+ memory t cells are il-15 dependent. | survival and intermittent proliferation of memory cd4(+) and cd8(+) t cells appear to be controlled by different homeostatic mechanisms. in particular, contact with interleukin (il)-15 has a decisive influence on memory cd8(+) cells, but not memory cd4(+) cells. past studies of memory cd4(+) cells have relied heavily on the use of naturally occurring memory phenotype (mp) cells as a surrogate for antigen (ag)-specific memory cells. however, we show here that mp cd4(+) cells contain a prominent s ... | 2007 | 17420265 |
| viral antigen and extensive division maintain virus-specific cd8 t cells during chronic infection. | efficient maintenance of memory cd8 t cells is central to long-term protective immunity. il-7- and il-15-driven homeostatic proliferation is essential for long-term memory cd8 t cell persistence after acute infections. during chronic infections, however, virus-specific cd8 t cells respond poorly to these cytokines. yet, virus-specific cd8 t cells often persist for long periods of time during chronic infections. we have addressed this apparent paradox by examining the mechanism for maintaining vi ... | 2007 | 17420267 |
| jinx, an mcmv susceptibility phenotype caused by disruption of unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis. | mouse cytomegalovirus (mcmv) susceptibility often results from defects of natural killer (nk) cell function. here we describe jinx, an n-ethyl-n-nitrosourea-induced mcmv susceptibility mutation that permits unchecked proliferation of the virus, causing death. in jinx homozygotes, activated nk cells and cytotoxic t lymphocytes (ctls) fail to degranulate, although they retain the ability to produce cytokines, and cytokine levels are markedly elevated in the blood of infected mutant mice. jinx was ... | 2007 | 17420270 |
| suppression of cell-mediated immunity by a donor-transmitted lymphocytic choriomeningitis virus in a kidney transplant recipient. | infection with lymphocytic choriomeningitis virus (lcmv) in rodents, the primary host, is known to cause suppression of cell-mediated immunity. serial determinations using a functional cell-mediated immune assay in a kidney transplant recipient with donor-transmitted lcmv also suggested profound suppression of cellular immunity. this suppression persisted in spite of reduction of immunosuppression. with the clearance of the virus there was reconstitution of the cellular immune response. | 2007 | 17428276 |
| serological survey of virus infection among wild house mice (mus domesticus) in the uk. | the serological prevalence of 13 murine viruses was surveyed among 103 wild-caught and 51 captive-bred house mice (mus domesticus), originating from several trapping locations in northwest england, using blood samples obtained during routine health screening of an established wild mouse colony. a high proportion of recently caught wild mice were seropositive for mouse hepatitis virus (86%), mouse cytomegalovirus (79%), mouse thymic virus (78%), mouse adenovirus (68%), mouse parvovirus (59%) and ... | 2007 | 17430622 |
| antigen presentation by nonhemopoietic cells amplifies clonal expansion of effector cd8 t cells in a pathogen-specific manner. | professional apcs of hemopoietic-origin prime pathogen-specific naive cd8 t cells. the primed cd8 t cells can encounter ag on infected nonhemopoietic cell types. whether these nonhemopoietic interactions perpetuate effector t cell expansion remains unknown. we addressed this question in vivo, using four viral and bacterial pathogens, by comparing expansion of effector cd8 t cells in bone marrow chimeric mice expressing restricting mhc on all cell types vs mice that specifically lack restricting ... | 2007 | 17442964 |
| a retroviral packaging cell line for pseudotype vectors based on glioma-infiltrating progenitor cells. | early clinical trials for gene therapy of human gliomas with retroviral packaging cells (pc) have been hampered by low transduction efficacy and lack of dissemination of pc within the tumor. in the current approach, these issues have been addressed by creating a stable packaging cell line for retroviral vectors pseudotyped with glycoproteins of lymphocytic choriomeningitis virus (lcmv) based on tumor-infiltrating progenitor cells. | 2007 | 17474071 |
| rapid and sustained cd4(+) t-cell-independent immunity from adenovirus-encoded vaccine antigens. | many novel vaccine strategies rely on recombinant viral vectors for antigen delivery, and adenovirus vectors have emerged among the most potent of these. in this report, we have compared the immune response induced through priming with adenovirus vector-encoded full-length viral protein to that elicited with an adenovirus-encoded minimal epitope covalently linked to beta(2)-microglobulin. we demonstrate that the beta(2)-microglobulin-linked epitope induced an accelerated and augmented cd8(+) t-c ... | 2007 | 17485530 |
| differential role of il-2r signaling for cd8+ t cell responses in acute and chronic viral infections. | il-2 is a cytokine with multiple and even divergent functions; it has been described as a key cytokine for in vitro t cell proliferation but is also essential for down-regulating t cell responses by inducing activation-induced cell death as well as regulatory t cells. the in vivo analysis of il-2 function in regulating specific t cell responses has been hampered by the fact that mice deficient in il-2 or its receptors develop lymphoproliferative diseases and/or autoimmunity. here we generated ch ... | 2007 | 17492805 |
| protracted course of lymphocytic choriomeningitis virus we infection in early life: induction but limited expansion of cd8+ effector t cells and absence of memory cd8+ t cells. | viral infections in human infants frequently follow a protracted course, with higher viral loads and delayed viral clearance compared to viral infections in older children. to identify the mechanisms responsible for this protracted pattern of infection, we developed an infant infection murine model using the well-characterized lymphocytic choriomeningitis virus (lcmv) we strain in 2-week-old balb/c mice. in contrast to adult mice, in which viral clearance occurred as expected 8 days after infect ... | 2007 | 17494081 |
| adenoviral vectors persist in vivo and maintain activated cd8+ t cells: implications for their use as vaccines. | cd8(+) t cell-numbers rapidly expand and then contract after exposure to their cognate antigen. here we show that the sustained frequencies of transgene product-specific cd8(+) t cells elicited by replication-defective adenovirus vectors are linked to persistence of low levels of transcriptionally active adenovirus vector genomes at the site of inoculation, in liver, and lymphatic tissues. continuously produced small amounts of antigen maintain fully active effector cd8(+) t cells, while also al ... | 2007 | 17510320 |
| analysis of the role of bleomycin hydrolase in antigen presentation and the generation of cd8 t cell responses. | long oligopeptides (>10 residues) are generated during the catabolism of cellular proteins in the cytosol. to be presented to t cells, such peptides must be trimmed by aminopeptidases to the proper size (typically 8-10 residues) to stably bind to mhc class i molecules. aminopeptidases also destroy epitopes by trimming them to even shorter lengths. bleomycin hydrolase (bh) is a cytosolic aminopeptidase that has been suggested to play a key role in generating mhc class i-presented peptides. we sho ... | 2007 | 17513741 |
| early blood profiles of virus infection in a monkey model for lassa fever. | acute arenavirus disease in primates, like lassa hemorrhagic fever in humans, begins with flu-like symptoms and leads to death approximately 2 weeks after infection. our goal was to identify molecular changes in blood that are related to disease progression. rhesus macaques (macaca mulatta) infected intravenously with a lethal dose of lymphocytic choriomeningitis virus (lcmv) provide a model for lassa virus infection of humans. blood samples taken before and during the course of infection were u ... | 2007 | 17522210 |
| mouse-to-human transmission of variant lymphocytic choriomeningitis virus. | a case of lymphocytic choriomeningitis virus (lcmv) infection led to investigation of the reservoir. lcmv was detected in mice trapped at the patient's home, and 12 isolates were recovered. genetic analysis showed that human and mouse lcmvs were identical and that this lcmv strain was highly divergent from previously characterized lcmv. | 2007 | 17552104 |
| clearance of an immunosuppressive virus from the cns coincides with immune reanimation and diversification. | once a virus infection establishes persistence in the central nervous system (cns), it is especially difficult to eliminate from this specialized compartment. therefore, it is of the utmost importance to fully understand scenarios during which a persisting virus is ultimately purged from the cns by the adaptive immune system. such a scenario can be found following infection of adult mice with an immunosuppressive variant of lymphocytic choriomeningitis virus (lcmv) referred to as clone 13. in th ... | 2007 | 17553158 |
| pet rodents and fatal lymphocytic choriomeningitis in transplant patients. | in april 2005, 4 transplant recipients became ill after receiving organs infected with lymphocytic choriomeningitis virus (lcmv); 3 subsequently died. all organs came from a donor who had been exposed to a hamster infected with lcmv. the hamster was traced back through a rhode island pet store to a distribution center in ohio, and more lcmv-infected hamsters were discovered in both. rodents from the ohio facility and its parent facility in arkansas were tested for the same lcmv strain as the 1 i ... | 2007 | 17553250 |
| hantavirus and arenavirus antibodies in persons with occupational rodent exposure. | rodents are the principal hosts of sin nombre virus, 4 other hantaviruses known to cause hantavirus pulmonary syndrome in north america, and the 3 north american arenaviruses. serum samples from 757 persons who had worked with rodents in north america and handled neotomine or sigmodontine rodents were tested for antibodies against sin nombre virus, whitewater arroyo virus, guanarito virus, and lymphocytic choriomeningitis virus. antibodies against sin nombre virus were found in 4 persons, agains ... | 2007 | 17553266 |
| congenital lymphocytic choriomeningitis virus infection: spectrum of disease. | lymphocytic choriomeningitis virus (lcmv) is a human pathogen and an emerging neuroteratogen. when the infection occurs during pregnancy, the virus can target and damage the fetal brain and retina. we examined the spectrum of clinical presentations, neuroimaging findings, and clinical outcomes of children with congenital lcmv infection. | 2007 | 17557350 |
| interleukin-10 plays an early role in generating virus-specific t cell anergy. | infection of mice with the armstrong strain of lymphocytic choriomeningitis virus (lcmvarm) leads to a robust immune response and efficient viral clearance. this is in contrast to infection with the variant strain lcmvclone13, which causes functional inactivation of effector t cells and viral persistence. the mechanism by which lcmvclone13 suppresses the antiviral immune response and persists in its host is unknown. | 2007 | 17570849 |
| peptide-activated double-negative t cells can prevent autoimmune type-1 diabetes development. | autoimmune diseases may develop because of defective maturation, activation, differentiation and function of regulatory t cells. previous studies have shown that exposure to donor antigen activates peripheral tcralphabeta+cd3+cd4-cd8-nk1.1-, double-negative (dn) t cells, which specifically suppress anti-donor t cells and enhance survival of skin and heart grafts from allogeneic and xenogeneic donors. however, the role of dn t cells in preventing t cell-mediated autoimmune disease is unknown. her ... | 2007 | 17578845 |
| arenavirus z-glycoprotein association requires z myristoylation but not functional ring or late domains. | generation of infectious arenavirus-like particles requires the virus ring finger z protein and surface glycoprotein precursor (gpc) and the correct processing of gpc into gp1, gp2, and a stable signal peptide (ssp). z is the driving force of arenavirus budding, whereas the gp complex (gpc), consisting of hetero-oligomers of ssp, gp1, and gp2, forms the viral envelope spikes that mediate receptor recognition and cell entry. based on the roles played by z and gp in the arenavirus life cycle, we h ... | 2007 | 17581989 |
| bim/bcl-2 balance is critical for maintaining naive and memory t cell homeostasis. | we examined the role of the antiapoptotic molecule bcl-2 in combating the proapoptotic molecule bim in control of naive and memory t cell homeostasis using bcl-2(-/-) mice that were additionally deficient in one or both alleles of bim. naive t cells were significantly decreased in bim(+/-)bcl-2(-/-) mice, but were largely restored in bim(-/-)bcl-2(-/-) mice. similarly, a synthetic bcl-2 inhibitor killed wild-type, but not bim(-/-), t cells. further, t cells from bim(+/-)bcl-2(-/-) mice died rapi ... | 2007 | 17591857 |
| preformed cd40 ligand exists in secretory lysosomes in effector and memory cd4+ t cells and is quickly expressed on the cell surface in an antigen-specific manner. | cd40 ligand (cd40l) is an essential effector cytokine for macrophage activation, dendritic cell licensing, and t-cell-dependent antibody responses. although cd40l is known to be made de novo following antigen recognition, several reports have described surface mobilization of preformed, intracellular cd40l in certain cd4(+) effector t cells. here we show that rapid surface expression of preformed cd40l following antigen recognition is a general property of both effector and memory cd4(+) t cells ... | 2007 | 17595332 |
| sequential polymicrobial infections lead to cns inflammatory disease: possible involvement of bystander activation in heterologous immunity. | vv(plp) is a recombinant vaccinia virus (vv) encoding myelin proteolipid protein (plp) that has been used to investigate molecular mimicry and autoimmunity. since virus infections can cause bystander activation, mice were first infected with vv(plp), and later challenged with wild-type vv, lymphocytic choriomeningitis virus (lcmv), or murine cytomegalovirus (mcmv). among the vv(plp)-primed mice, only mcmv challenge induced significant ki-67(+), cd3(+)t cell infiltration into the central nervous ... | 2007 | 17604850 |
| lymphocytic choriomeningitis infection undetected by dirty-bedding sentinel monitoring and revealed after embryo transfer of an inbred strain derived from wild mice. | persistent lcmv infection in wild-derived mai/pas mice housed under conventional conditions remained undetected for a decade, despite periodic health monitoring using dirty-bedding sentinels. when mai/pas mice were rederived by embryo transfer, recipient mothers produced antilcmv antibodies, which first revealed the presence of the virus in the colony. before this information was obtained, mai/pas mice had been shipped to another facility, undergone cesarean rederivation there, and been introduc ... | 2007 | 17605342 |
| simian immunodeficiency virus vector pseudotypes differ in transduction efficiency and target cell specificity in brain. | lentiviral vectors have proven to be promising tools for transduction of brain cells in vivo and in vitro. in this study, we have examined the central nervous system (cns) transduction efficiencies and patterns of a self-inactivating simian immunodeficiency virus (sivmac)-derived lentiviral vector pseudotyped with glycoproteins from the vesicular stomatitis virus (vsv-g), the amphotropic murine leukemia virus (mlv4070aenv), the lymphocytic choriomeningitis virus (lcmv-gp), the ross river virus ( ... | 2007 | 17611586 |
| chronic lymphocytic choriomeningitis virus infection actively down-regulates cd4+ t cell responses directed against a broad range of epitopes. | activation of cd4(+) t cells helps establish and sustain cd8(+) t cell responses and is required for the effective clearance of acute infection. cd4-deficient mice are unable to control persistent infection and cd4(+) t cells are usually defective in chronic and persistent infections. we investigated the question of how persistent infection impacted pre-existing lymphocytic choriomeningitis virus (lcmv)-specific cd4(+) t cell responses. we identified class ii-restricted epitopes from the entire ... | 2007 | 17617598 |
| direct interferon-gamma signaling dramatically enhances cd4+ and cd8+ t cell memory. | studies in ifn-gamma-deficient mice suggest that the delivery of ifn-gamma to cd8(+) t cells early in virus infection programs their eventual contraction, thereby reducing the abundance of cd8(+) memory t cells. in this study, we show that such mice fail to completely eliminate virus infection and that, when evaluated without the confounding factor of persisting ag, both cd4(+) and cd8(+) t cells undergo profound contraction when they are unable to receive ifn-gamma signals. furthermore, the abu ... | 2007 | 17617612 |
| ccr5 and cxcr3 are dispensable for liver infiltration, but ccr5 protects against virus-induced t-cell-mediated hepatic steatosis. | ccr5 and cxcr3 are important molecules in regulating the migration of activated lymphocytes. thus, the majority of tissue-infiltrating t cells found in the context of autoimmune conditions and viral infections express ccr5 and cxcr3, and the principal chemokine ligands are expressed within inflamed tissues. accordingly, intervention studies have pointed to nonredundant roles of these receptors in models of allograft rejection, viral infection, and autoimmunity. in spite of this, considerable con ... | 2007 | 17626099 |
| development of recombinant nucleoprotein-based diagnostic systems for lassa fever. | diagnostic systems for lassa fever (lf), a viral hemorrhagic fever caused by lassa virus (lasv), such as enzyme immunoassays for the detection of lasv antibodies and lasv antigens, were developed using the recombinant nucleoprotein (rnp) of lasv (lasv-rnp). the lasv-rnp was expressed in a recombinant baculovirus system. lasv-rnp was used as an antigen in the detection of lasv-antibodies and as an immunogen for the production of monoclonal antibodies. the lasv-rnp was also expressed in hela cells ... | 2007 | 17634509 |
| cd8 t cell dysfunction during chronic viral infection. | clearance of primary infection often leads to the development of highly functional memory t cells capable of rapid and long-lasting protective immunity. by contrast, chronic infections can result in t cell dysfunction and poor pathogen control. in this review, we will discuss recent work that highlights two main types of t cell dysfunction during chronic infection: exhaustion of effector functions and altered memory t cell development. | 2007 | 17656078 |
| decreased tumor surveillance after adoptive t-cell therapy. | the effect of cancer immunotherapy on the endogenous immune response against tumors is largely unknown. therefore, we studied immune responses against murine tumors expressing the glycoprotein (gp) and/or nucleoprotein of lymphocytic choriomeningitis virus (lcmv) with or without adoptive t-cell therapy. in nontreated animals, ctls specific for different epitopes as well as lcmv-gp-specific antibodies contributed to tumor surveillance. adoptive immunotherapy with monoclonal ctls specific for lcmv ... | 2007 | 17671217 |
| regulation of homeostatic chemokine expression and cell trafficking during immune responses. | the chemokines ccl21 and cxcl13 are immune factors that dictate homing and motility of lymphocytes and dendritic cells in lymphoid tissues. however, the means by which these chemokines are regulated and how they influence cell trafficking during immune responses remain unclear. we show that ccl21 and cxcl13 are transiently down-regulated within lymphoid tissues during immune responses by a mechanism controlled by the cytokine interferon-gamma. this modulation was found to alter the localization ... | 2007 | 17673664 |
| role of direct effects of ifn-gamma on t cells in the regulation of cd8 t cell homeostasis. | it is well recognized that ifn-gamma plays a critical role in the control of cd8 t cell expansion and contraction during immune responses to several intracellular pathogens. however, our understanding of the mechanisms underlying the regulation of t cell fate by ifn-gamma is sorely incomplete. specifically, it is unclear whether regulation of cd8 t cell homeostasis occurs by a t cell intrinsic ifn-gamma pathway. in this study, we have determined the role of the direct effects of ifn-gamma on t c ... | 2007 | 17675470 |
| chronic immunodeficiency in mice lacking rasgrp1 results in cd4 t cell immune activation and exhaustion. | the ras-guanyl nucleotide exchange factor rasgrp1 is an important link between tcr-mediated signaling and the activation of ras and its downstream effectors. rasgrp1 is especially critical for the survival and differentiation of developing thymocytes whereas negative selection of thymocytes bearing an autoreactive tcr appears to be rasgrp1 independent. despite apparently normal central tolerance, rasgrp1(-/-) mice spontaneously acquire an acutely activated and proliferating cd4 t cell population ... | 2007 | 17675473 |
| fully mhc-disparate mixed hemopoietic chimeras show specific defects in the control of chronic viral infections. | the establishment of mixed allogeneic chimerism can induce donor-specific transplantation tolerance across full mhc barriers. however, a theoretical disadvantage of this approach is the possibility that the state of mixed chimerism might negatively affect the recipient's immune competence to control pathogens. previous studies using murine models have not supported this hypothesis, because they indicate that acute viral infections are cleared by chimeric animals with similar kinetics to that of ... | 2007 | 17675525 |