| activation of tyk2 and stat3 is required for the apoptotic actions of interferon-beta in primary pro-b cells. | the growth-inhibitory effects of type 1 interferons (ifns) (ifnalpha/beta) are complex, and the role of apoptosis in their antigrowth effects is variable and not well understood. we have examined primary murine interleukin-7-dependent bone marrow-derived pro-b cells, where ifnbeta, but not ifnalpha, induces programmed cell death (pcd). ifnbeta-stimulated apoptosis is the same in pro-b cells derived from wild type and stat1(-/-) mice. however, in pro-b cells from tyk2(-/-) mice, where there is no ... | 2006 | 16601124 |
| arenavirus z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds. | several disulfide-based and azoic compounds have shown antiviral and virucidal properties against arenaviruses in virus yield-inhibition and inactivation assays, respectively. the most effective virucidal agent, the aromatic disulfide nsc20625, was able to inactivate two strains of the prototype arenavirus species lymphocytic choriomeningitis virus (lcmv). inactivated viral particles retained the biological functions of the virion envelope glycoproteins in virus binding and uptake, but were unab ... | 2006 | 16603524 |
| "viral déjà vu" elicits organ-specific immune disease independent of reactivity to self. | autoimmune diseases are often precipitated by viral infections. yet our current understanding fails to explain how viruses trigger organ-specific autoimmunity despite thymic tolerance extending to many non-lymphohematopoietic self antigens. additionally, a key epidemiological finding needs to be explained: in genetically susceptible individuals, early childhood infections seem to predispose them to multiple sclerosis (ms) or type 1 diabetes years or even decades before clinical onset. in the pre ... | 2006 | 16604192 |
| lambda interferon (ifn-lambda), a type iii ifn, is induced by viruses and ifns and displays potent antiviral activity against select virus infections in vivo. | type iii interferons (ifns) (interleukin-28/29 or lambda interferon [ifn-lambda]) are cytokines with ifn-like activities. here we show that several classes of viruses induce expression of ifn-lambda1 and -lambda2/3 in similar patterns. the ifn-lambdas were-unlike alpha/beta interferon (ifn-alpha/beta)-induced directly by stimulation with ifn-alpha or -lambda, thus identifying type iii ifns as ifn-stimulated genes. in vitro assays revealed that ifn-lambdas have appreciable antiviral activity agai ... | 2006 | 16611910 |
| narrowed tcr repertoire and viral escape as a consequence of heterologous immunity. | why some virus-specific cd8 tcr repertoires are diverse and others restricted or "oligoclonal" has been unknown. we show here that oligoclonality and extreme clonal dominance can be a consequence of t cell cross-reactivity. lymphocytic choriomeningitis virus (lcmv) and pichinde virus (pv) encode np(205-212) epitopes that induce different but highly cross-reactive diverse tcr repertoires. homologous viral challenge of immune mice only slightly skewed the repertoire and enriched for predictable tc ... | 2006 | 16614754 |
| survey of lymphocytic choriomeningitis virus diagnosis and testing--connecticut, 2005. | lymphocytic choriomeningitis virus (lcmv) is a rodent borne virus that can be transmitted to humans through exposure to rodent urine, feces, saliva, or blood. lcmv infection is often asymptomatic or mild but can cause aseptic meningitis, encephalitis, life-threatening infections in immunosuppressed persons, and severe congenital defects . in may 2005, lcmv was implicated in the deaths of three organ transplant recipients who had received organs from a common donor who had likely been infected fr ... | 2006 | 16617288 |
| serine protease inhibitor 6 protects cytotoxic t cells from self-inflicted injury by ensuring the integrity of cytotoxic granules. | how cytotoxic t lymphocytes (ctls) kill intracellular pathogens without killing themselves has been a recurring question ever since their discovery. by using mice deficient in serine protease inhibitor 6 (spi6), we show that by inhibiting granzyme b (grb), spi6 protects ctls from self-inflicted injury. infection with either lymphocytic choriomeningitis virus (lcmv) or listeria monocytogenes (lm) revealed increased apoptosis and diminished survival of spi6 knockout (ko) ctls, which was cell auton ... | 2006 | 16618603 |
| role of very late antigen-1 in t-cell-mediated immunity to systemic viral infection. | the t-cell response to lymphocytic choriomeningitis virus was studied in mice lacking very late antigen-1 (vla-1). the generation of virus-specific effector t cells was unimpaired in vla-1(-/-) mice. in the memory phase, vla-1 deficiency did not influence the number of memory cd8(+) t cells or their distribution between lymphoid and nonlymphoid organs. regarding a functional role of vla-1, we found that intracerebral infection of both vla-1(-/-) and wild-type (wt) mice resulted in lethal t-cell- ... | 2006 | 16623929 |
| reviving exhausted t lymphocytes during chronic virus infection by b7-h1 blockade. | cytotoxic t lymphocytes (ctls) are killer cells that are crucial in the control of viral pathogens and cancers. they can become exhausted during chronic viral infection, a phenomenon that consists of a reduction in both number and functionality of ctls. recently, barber and colleagues demonstrated that b7-h1 (also called pd-l1), a cell-surface molecule that is widely distributed in tissues, was necessary for the maintenance of t-cell exhaustion in a chronic-infection mouse model of lymphocytic c ... | 2006 | 16650803 |
| lymphocytic choriomeningitis in michigan. | we summarize the first reported case of acquired lymphocytic choriomeningitis virus (lcmv) infection in michigan to be investigated by public health authorities and provide evidence of the focal nature of lcmv infection in domestic rodents. results of serologic and virologic testing in rodents contrasted, and negative serologic test results should be confirmed by tissue testing. | 2006 | 16704853 |
| an altered t cell repertoire in mecl-1-deficient mice. | immunoproteasome subunits low-molecular mass polypeptide (lmp)2 and lmp7 affect ag presentation by mhc class i molecules. in the present study, we investigated the function of the third immunosubunit lmp10/multicatalytic endopeptidase complex-like (mecl)-1 (beta2i) in mecl-1 gene-targeted mice. the number of cd8+ splenocytes in mecl-1-/- mice was 20% lower than in wild-type mice. infection with lymphocytic choriomeningitis virus (lcmv) elicited a markedly reduced cytotoxic t cell (ctl) response ... | 2006 | 16709825 |
| lymphocytic choriomeningitis virus--an old enemy up to new tricks. | | 2006 | 16723613 |
| transmission of lymphocytic choriomeningitis virus by organ transplantation. | in december 2003 and april 2005, signs and symptoms suggestive of infection developed in two groups of recipients of solid-organ transplants. each cluster was investigated because diagnostic evaluations were unrevealing, and in each a common donor was recognized. | 2006 | 16723615 |
| lymphocytic choriomeningitis virus: an emerging obstetric pathogen? | a report in may 2005 from the centers for disease control and prevention describing a cluster of lymphocytic choriomeningitis virus (lcmv) infections among 4 solid organ recipients has increased awareness of and clinical interest in this pathogen. human infection with lcmv results from direct or indirect contact with rodents. lcmv has particular relevance to obstetrics, as it is likely an under-recognized abortifacient and fetal teratogen. there have been 54 cases of congenital lcmv reported sin ... | 2006 | 16731068 |
| identification of an n-terminal trimeric coiled-coil core within arenavirus glycoprotein 2 permits assignment to class i viral fusion proteins. | the lymphocytic choriomeningitis virus (lcmv) glycoprotein (gp) consists of the transmembrane subunit gp-2 and the receptor binding subunit gp-1. both are synthesized as one precursor protein and stay noncovalently attached after cleavage. in this study, we determined the oligomeric state of the lcmv gp and expressed it in two different conformations suitable for structural analysis. sequence analysis of gp-2 identified a trimeric heptad repeat pattern containing an n-terminal alpha-helix. an al ... | 2006 | 16731928 |
| congenital lymphocytic choriomeningitis virus: an underdiagnosed cause of neonatal hydrocephalus. | we report a case of congenital hydrocephalus caused by lymphocytic choriomeningitis virus with severe neurologic sequelae, including hydrocephalus, chorioretinitis, blindness and developmental delay. this is the first report of lymphocytic choriomeningitis virus isolation in the cerebrospinal fluid of a congenitally infected infant. | 2006 | 16732159 |
| strong tcr signaling, tlr ligands, and cytokine redundancies ensure robust development of type 1 effector t cells. | t cell effector function is a central mechanism of adaptive immunity, and accordingly, protection of the host against pathogens. one of the primary effector molecules produced by t cells in response to such pathogens is the cytokine, ifn-gamma. although the signaling pathways associated with the production of ifn-gamma are well established, disparate in vivo and in vitro results indicate that distinct pathways may become more prominent dependent upon the nature of the infection, inflammatory mil ... | 2006 | 16751361 |
| envelope exchange for the generation of live-attenuated arenavirus vaccines. | arenaviruses such as lassa fever virus cause significant mortality in endemic areas and represent potential bioterrorist weapons. the occurrence of arenaviral hemorrhagic fevers is largely confined to third world countries with a limited medical infrastructure, and therefore live-attenuated vaccines have long been sought as a method of choice for prevention. yet their rational design and engineering have been thwarted by technical limitations. in addition, viral genes had not been identified tha ... | 2006 | 16751848 |
| bim mediates apoptosis of cd127(lo) effector t cells and limits t cell memory. | following an acute t cell response, most activated effector cells die, while some survive and become memory cells. the pro-apoptotic bcl-2 family member, bcl-2 interacting mediator of death (bim) is critical for eliminating most effector t cells, while expression of cd127 (il-7ralpha) has been proposed to mark effector cells destined to become memory cells. here, we examined the effects of bim on the death of effector t cells in relationship to cd127 expression and on development of t cell memor ... | 2006 | 16761315 |
| simultaneous assessment of antigen-stimulated cytokine production and memory subset composition of memory cd8 t cells. | the functional identification of antigen-specific cd8 t cell populations is critical to understanding host responses to infection by intracellular pathogens. furthermore, assessing the properties of protective memory cd8 t cell populations generated by immunization is necessary in the rational design of vaccines. recently, a classification scheme was proposed in which memory cd8 t cells were divided into one of two distinct subsets, based on cd62l expression, that have different functional prope ... | 2006 | 16762359 |
| hypogammaglobulinemia and exacerbated cd8 t-cell-mediated immunopathology in sap-deficient mice with chronic lcmv infection mimics human xlp disease. | the human genetic disease x-linked lymphoproliferative disease (xlp), which is caused by mutations in sh2d1a/sap that encode slam-associated protein (sap), is characterized by an inability to control epstein-barr virus (ebv) and hypogammaglobulinemia. it is unclear which aspects of xlp disease are specific to herpesvirus infection and which reflect general immunologic functions performed by sap. we examined sap- mice during a chronic lcmv infection, specifically to address the following question ... | 2006 | 16788096 |
| receptor use by pathogenic arenaviruses. | the arenavirus family contains several important human pathogens including lassa fever virus (lasv), lymphocytic choriomeningitis virus (lcmv) and the new world clade b viruses junin (junv) and machupo (macv). previously, alpha-dystroglycan (alpha-dg) was identified as a receptor recognized by lasv and certain strains of lcmv. however, other studies have suggested that alpha-dg is probably not used by the clade b viruses, and the receptor(s) for these pathogens is currently unknown. using pseudo ... | 2006 | 16797051 |
| a role for the transcription factor relb in ifn-alpha production and in ifn-alpha-stimulated cross-priming. | chimeric mice generated with bone marrow from relb-deficient (-/-), relb-heterozygous (+/-) and wild-type (+/+) mice were used to determine how total or partial absence of the transcription factor relb in haematopoietic cells affects the immune response generated after lymphocytic choriomeningitis virus (lcmv) infection. in relb(-/-) chimeras, early virus replication was enhanced and lcmv clearance was impaired. although plasmacytoid dendritic cell numbers were similar, serum interferon (ifn)-al ... | 2006 | 16810633 |
| immune response to vaccination against argentine hemorrhagic fever in an area where different arenaviruses coexist. | neutralizing antibody (nt ab) titers to candid #1 (c#1) vaccine against argentine hemorrhagic fever were studied for 2 years post-vaccination in 330 volunteers, to assess whether the kinetics and/or magnitude of this immune response is modified by previous infection with the arena viruses junin (jun) and lymphocytic choriomeningitis (lcm). a total of 160 volunteers received c#1, distributed as follows: without detectable pre-infection with arenaviruses (n = 54); with pre-existing antibodies to j ... | 2006 | 16817762 |
| electron transport complex i is required for cd8+ t cell function. | after ag encounter, cd8+ t cells become activated and begin to proliferate. early during infection, when ag-specific effector cd8+ t cells are proliferating, producing cytokines, and lysing infected cells in vivo, their mitochondrial potential is increased. the purpose of the experiments presented here was to determine whether mitochondrial function was required for cd8+ t cell function. to block mitochondrial function, transgenic cd8+ t cells were incubated with increasing doses of rotenone, an ... | 2006 | 16818739 |
| trail deficiency delays, but does not prevent, erosion in the quality of "helpless" memory cd8 t cells. | in this study, we investigated the role of trail in ag-specific cd8 t cell homeostasis after viral infection. trail deficiency does not influence the kinetics of the ag-specific cd8 t cell responses, and cd8 t cells in trail-deficient mice were able to expand, contract, and generate functional memory cell numbers that were indistinguishable from trail-sufficient wild-type cd8 t cells after acute lymphocytic choriomeningitis virus infection. interestingly, the ability of "helpless" cd8 t cells to ... | 2006 | 16818756 |
| 5,6-dimethylxanthenone-4-acetic acid treatment of a non-immunogenic tumour does not synergize with active or passive cd8+ t-cell immunotherapy. | the chemotherapeutic drug 5,6-dimethylxanthenone-4-acetic acid (dmxaa) inhibits intratumoural blood flow, causing hypoxia, haemorrhagic necrosis, vascular collapse and tumour cell death. production of tnf-alpha and ifn is also induced, causing local inflammation and activation of immune cells including cd8+ t cells. we used the tumour cell line ll-lcmv, which expresses the gp33 epitope of lymphocytic choriomeningitis virus in a non-immunogenic form, to investigate whether tumour cell death cause ... | 2006 | 16834573 |
| expression of ccl20 and granulocyte-macrophage colony-stimulating factor, but not flt3-l, from modified vaccinia virus ankara enhances antiviral cellular and humoral immune responses. | while modified vaccinia virus ankara (mva) is currently in clinical development as a safe vaccine against smallpox and heterologous infectious diseases, its immunogenicity is likely limited due to the inability of the virus to replicate productively in mammalian hosts. in light of recent data demonstrating that vaccinia viruses, including mva, preferentially infect antigen-presenting cells (apcs) that play crucial roles in generating antiviral immunity, we hypothesized that expression of specifi ... | 2006 | 16840346 |
| expression of lymphotoxin beta governs immunity at two distinct levels. | interaction of lymphotoxin alpha(1)beta(2) (ltalpha(1)beta(2)) with its receptor is key for the generation and maintenance of secondary lymphoid organ microstructure. we used mice conditionally deficient for ltbeta on different lymphocyte subsets to determine how the ltbeta-dependent lymphoid structure influences immune reactivity. all conditionally ltbeta-deficient mice mounted normal immune responses against vesicular stomatitis virus (vsv), and were protected against lymphocytic choriomeningi ... | 2006 | 16841297 |
| hereditary hydrocephalus in laboratory-reared golden hamsters (mesocricetus auratus). | a colony of golden hamsters had an ongoing problem with hydrocephalus. in an attempt to clear the colony of the problem, new breeders from another supplier had been purchased. at termination of a behavioral study, the brain was collected from 35 animals (four of which had died with hydrocephalus during the study) and was examined macroscopically and by light microscopy. although no animals manifested obvious behavioral changes, 31 of 35 (88.6%, 13/15 males and 18/20 females in control and manipu ... | 2006 | 16846994 |
| adoptive immunotherapy induces cns dendritic cell recruitment and antigen presentation during clearance of a persistent viral infection. | given the global impact of persistent infections on the human population, it is of the utmost importance to devise strategies to noncytopathically purge tissues of infectious agents. the central nervous system (cns) poses a unique challenge when considering such strategies, as it is an immunologically specialized compartment that contains a nonreplicative cell population. administration of exogenously derived pathogen-specific memory t cells (referred to as adoptive immunotherapy) to mice burden ... | 2006 | 16847068 |
| innate inflammatory signals induced by various pathogens differentially dictate the ifn-i dependence of cd8 t cells for clonal expansion and memory formation. | type-i ifns (ifn-i) provide direct survival signals to t cells during ag-driven proliferation. because ifn-i production differs depending on the pathogen, we assessed cd8 t cell requirement for direct ifn-i signals during responses to vaccinia virus (vv), vesicular stomatitis virus (vsv), lymphocytic choriomeningitis virus (lcmv), and listeria monocytogenes (lm) immunizations in vivo. ifn-i-receptor-deficient (ifn-ir(o)) cd8 t cells expanded 3- to 5-fold less and formed a diminished memory pool ... | 2006 | 16849484 |
| cd45 is required for type i ifn production by dendritic cells. | cd45 is a leukocyte tyrosine phosphatase, essential for normal immune responses. we have studied the function of splenic dendritic cells of cd45(+/+), cd45(-/-), cd45rabc and cd45ro transgenic mice. we show that there are increased numbers of plasmacytoid dendritic cells in cd45(-/-) mice. dc of all mice are capable of responding to lymphocytic choriomeningitis virus (lcmv) infection by up-regulation of mhc and costimulatory molecules. dc of cd45(-/-) mice have an impaired capacity to produce ty ... | 2006 | 16856204 |
| imatinib mesylate selectively impairs expansion of memory cytotoxic t cells without affecting the control of primary viral infections. | imatinib mesylate (imatinib) is a potent inhibitor of defined tyrosine kinases (tks) and is effective in the treatment of malignancies characterized by constitutive activation of these tks such as chronic myeloid leukemia and gastrointestinal stromal tumors. tks also play an important role in t-cell receptor (tcr) signal transduction. inhibitory as well as stimulating effects of imatinib on t cells and dendritic cells have been described. here, we analyzed the effects of imatinib treatment on an ... | 2006 | 16873671 |
| t cells with low avidity for a tissue-restricted antigen routinely evade central and peripheral tolerance and cause autoimmunity. | t cells causing autoimmunity must escape tolerance. we observed that cd8(+) t cells with high avidity for an antigen expressed in the pancreas, kidney, and thymic medulla were efficiently removed from a polyclonal repertoire by central and peripheral tolerance mechanisms. however, both mechanisms spared low-avidity t cells from elimination. neither the introduction of activated, self-antigen-specific cd4(+) helper t cells nor a global inflammatory stimulus were sufficient to activate the low-avi ... | 2006 | 16879996 |
| nonneutralizing antibodies binding to the surface glycoprotein of lymphocytic choriomeningitis virus reduce early virus spread. | the biological relevance of nonneutralizing antibodies elicited early after infection with noncytopathic persistence-prone viruses is unclear. we demonstrate that cytotoxic t lymphocyte-deficient tgh(kl25) mice, which are transgenic for the heavy chain of the lymphocytic choriomeningitis virus (lcmv)-neutralizing monoclonal antibody kl25, mount a focused neutralizing antibody response following lcmv infection, and that this results in the emergence of neutralization escape virus variants. furthe ... | 2006 | 16880253 |
| role of bim in regulating cd8+ t-cell responses during chronic viral infection. | apoptosis is critical for the development and maintenance of the immune system. the proapoptotic bcl-2 family member bim is important for normal immune system homeostasis. although previous experiments have shown that bim is critical for the apoptosis of antigen-specific cd8(+) t cells during acute viral infection, the role of bim during chronic viral infection is unclear. using lymphocytic choriomeningitis virus clone 13 infection of mice, we demonstrate a role for bim in cd8(+) t-cell apoptosi ... | 2006 | 16912311 |
| generation and characterization of b7-h4/b7s1/b7x-deficient mice. | members of the b7 family of cosignaling molecules regulate t-cell proliferation and effector functions by engaging cognate receptors on t cells. in vitro and in vivo blockade experiments indicated that b7-h4 (also known as b7s1 or b7x) inhibits proliferation, cytokine production, and cytotoxicity of t cells. b7-h4 binds to an unknown receptor(s) that is expressed on activated t cells. however, whether b7-h4 plays nonredundant immune regulatory roles in vivo has not been tested. we generated b7-h ... | 2006 | 16914726 |
| the evolving epidemiology of viral encephalitis. | the introduction of west nile virus to north america illustrates the potential emergence of novel encephalitic agents in unexpected settings. there has been continued recognition of emerging neurotropic viruses in both the developed and developing world and novel modes of transmission of these agents. this review describes recent developments in the epidemiology of west nile virus and several other emerging viral encephalitides in the developed and developing world and the emergence of novel mec ... | 2006 | 16914972 |
| upregulation of pd-1 expression on hiv-specific cd8+ t cells leads to reversible immune dysfunction. | the engagement of programmed death 1 (pd-1) to its ligands, pd-l1 and pd-l2, inhibits proliferation and cytokine production mediated by antibodies to cd3 (refs. 5,6,7). blocking the pd-1-pd-l1 pathway in mice chronically infected with lymphocytic choriomeningitis virus restores the capacity of exhausted cd8(+) t cells to undergo proliferation, cytokine production and cytotoxic activity and, consequently, results in reduced viral load. during chronic hiv infection, hiv-specific cd8(+) t cells are ... | 2006 | 16917489 |
| type 1 ifn deficiency in the absence of normal splenic architecture during lymphocytic choriomeningitis virus infection. | the innate immune system uses different mechanisms to respond to infectious pathogens. experiments evaluating the requirements for a type 1 ifn (ifn-alphabeta) response to lymphocytic choriomeningitis virus (lcmv) resulted in the surprising discovery that mice deficient in b and t cell development, i.e., rag-deficient and scid, had profoundly reduced levels of ifn-alphabeta in serum and spleen, despite high viral replication. in addition to lacking an adaptive immune system, these strains exhibi ... | 2006 | 16920967 |
| dendritic cell inhibition: memoirs from immunosuppressive viruses. | | 2006 | 16921469 |
| elimination of chronic viral infection by blocking cd27 signaling. | neutralizing antibody (nab) responses to lymphocytic choriomeningitis virus (lcmv) in mice and immunodeficiency virus and hepatitis c virus in humans are usually weak and slow to develop. this may be the result of structural properties of the surface glycoprotein, a low frequency of b cells with neutralizing specificity, and the necessity of prolonged affinity maturation of specific nabs. in this study, we show that during lcmv infection, cd27 signaling on cd4+ t cells enhances the secretion of ... | 2006 | 16923852 |
| direct stimulation of t lymphocytes by immunosomes: virus-like particles decorated with t cell receptor/cd3 ligands plus costimulatory molecules. | many infectious viruses coevolved with the vertebrate immune system. during the assembly of enveloped viruses, lipid ordered domains of the host cell plasma membrane, called lipid rafts, frequently function as a natural meeting point for viral proteins. the role of lipid rafts in the organization of complex combinations of immune receptors during antigen presentation and t cell signaling is widely recognized. in our studies, we determined whether lipid rafts, virus budding, and molecular interac ... | 2006 | 16924110 |
| altered central nervous system gene expression caused by congenitally acquired persistent infection with lymphocytic choriomeningitis virus. | neonatal infection of most mouse strains with lymphocytic choriomeningitis virus (lcmv) leads to a life-long persistent infection characterized by high virus loads in the central nervous system (cns) in the absence of inflammation and tissue destruction. these mice, however, exhibit impaired learning and memory. the occurrence of cognitive defects in the absence of overt cns pathology led us to the hypothesis that chronic virus infection may contribute to neuronal dysfunction by altering the hos ... | 2006 | 16940520 |
| inhibition of the type i interferon response by the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus. | the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) is a formidable battle horse for the study of viral immunology, as well as viral persistence and associated diseases. investigations with lcmv have uncovered basic mechanisms by which viruses avoid elimination by the host adaptive immune response. in this study we show that lcmv also disables the host innate defense by interfering with beta interferon (ifn-beta) production in response to different stimuli, including infection wi ... | 2006 | 16940530 |
| different neurotropic pathogens elicit neurotoxic ccr9- or neurosupportive cxcr3-expressing microglia. | what mechanism that determines microglia accomplishing destructive or constructive role in cns remains nebulous. we report here that intracranial priming and rechallenging with toxoplasma gondii in mice elicit neurotoxic ccr9+ irg1+ (immunoresponsive gene 1) microglia, which render resistance to apoptosis and produce a high level of tnf-alpha; priming and rechallenging with lymphocytic choriomeningitis virus elicit neurosupportive cxcr3+ irg1- microglia, which are sensitive to apoptosis and prod ... | 2006 | 16951324 |
| transgenic expression of the viral flip mc159 causes lpr/gld-like lymphoproliferation and autoimmunity. | death receptor-induced programmed cell death (pcd) is crucial for the maintenance of immune homeostasis. however, interference of downstream death receptor signaling by genetic ablation or transgenic (tg) expression of different apoptosis inhibitors often impairs lymphocyte activation. the viral flice (caspase-8)-like inhibitor proteins (v-flips) are potent inhibitors of death receptor-induced apoptosis and programmed necrosis. we generated tg mice expressing the v-flip mc159 from molluscum cont ... | 2006 | 16951343 |
| impaired memory cd8 t cell development in the absence of methyl-cpg-binding domain protein 2. | intracellular differentiation events that determine which cells develop into memory cd8 t cells are currently incompletely understood. methyl-cpg-binding domain protein 2 (mbd2) is a transcriptional repressor that binds to methylated dna and mediates the biological consequences of epigenetic gene methylation. the role of mbd2 during the differentiation of naive cd8 t cells into effector and memory cells was determined following acute infection of mbd2-deficient mice with lymphocytic choriomening ... | 2006 | 16951344 |
| listeriolysin o-deficient listeria monocytogenes as a vaccine delivery vehicle: antigen-specific cd8 t cell priming and protective immunity. | strains of listeria monocytogenes (lm) that are deficient in the virulence factor listeriolysin o (llo) are highly attenuated and are thought not to elicit protective immunity. this failure has been attributed to the inability of the bacterium to enter the host cell cytosol and access mhc class i ag processing machinery. we reexamined this issue using recombinant strains of lm that are deficient in llo but express an additional cd8 t cell epitope derived from lymphocytic choriomeningitis virus. ... | 2006 | 16951364 |
| continuous recruitment of naive t cells contributes to heterogeneity of antiviral cd8 t cells during persistent infection. | numerous microbes establish persistent infections, accompanied by antigen-specific cd8 t cell activation. pathogen-specific t cells in chronically infected hosts are often phenotypically and functionally variable, as well as distinct from t cells responding to nonpersistent infections; this phenotypic heterogeneity has been attributed to an ongoing reencounter with antigen. paradoxically, maintenance of memory cd8 t cells to acutely resolved infections is antigen independent, whereas there is a ... | 2006 | 16966427 |
| augmented il-7 signaling during viral infection drives greater expansion of effector t cells but does not enhance memory. | il-7 signals are crucial for the survival of naive and memory t cells, and the il-7r is expressed on the surface of these cells. following viral infection, the il-7r is expressed on only a subset of effector cd8 t cells, and has been demonstrated to be important for the survival of these memory precursors. il-7 message levels remain relatively constant during the t cell response to lymphocytic choriomeningitis virus, but a short-lived burst of gm-csf is observed soon after infection. retroviral ... | 2006 | 16982881 |
| hiv: tired t cells turn around. | | 2006 | 16988698 |
| reinvigorating exhausted hiv-specific t cells via pd-1-pd-1 ligand blockade. | the programmed death (pd)-1-pd-1 ligand (pd-l) pathway, which is part of the b7-cd28 family, consists of the pd-1 receptor and its two ligands pd-l1 and pd-l2. engagement of pd-1 by its ligands inhibits immune responses, and recent work has shown that pd-1 is highly expressed on exhausted t cells during chronic lymphocytic choriomeningitis virus (lcmv) infection in mice. blockade of this pathway reinvigorates the exhausted t cells, allowing them to expand and produce effector cytokines, raising ... | 2006 | 17000870 |
| another donor derived pathogen to watch out for. | | 2006 | 17001758 |
| 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 |
| increased susceptibility to bacterial superinfection as a consequence of innate antiviral responses. | the reason why severe localized or systemic virus infections enhance and aggravate bacterial superinfection is poorly understood. here we show that virus-induced ifn type i caused apoptosis in bone marrow granulocytes, drastically reduced granulocyte infiltrates at the site of bacterial superinfection, caused up to 1,000-fold higher bacterial titers in solid organs, and increased disease susceptibility. the finding that the innate antiviral immune response reduces the antibacterial granulocyte d ... | 2006 | 17030789 |
| acquired hydrocephalus caused by a variant lymphocytic choriomeningitis virus. | | 2006 | 17030840 |
| resolution of a chronic viral infection after interleukin-10 receptor blockade. | a defining characteristic of persistent viral infections is the loss and functional inactivation of antiviral effector t cells, which prevents viral clearance. interleukin-10 (il-10) suppresses cellular immune responses by modulating the function of t cells and antigen-presenting cells. in this paper, we report that il-10 production is drastically increased in mice persistently infected with lymphocytic choriomeningitis virus. in vivo blockade of the il-10 receptor (il-10r) with a neutralizing a ... | 2006 | 17030951 |
| interleukin-10 determines viral clearance or persistence in vivo. | persistent viral infections are a major health concern. one obstacle inhibiting the clearance of persistent infections is functional inactivation of antiviral t cells. although such immunosuppression occurs rapidly after infection, the mechanisms that induce the loss of t-cell activity and promote viral persistence are unknown. herein we document that persistent viral infection in mice results in a significant upregulation of interleukin (il)-10 by antigen-presenting cells, leading to impaired t ... | 2006 | 17041596 |
| socs-1 protects from virally-induced cd8 t cell mediated type 1 diabetes. | cd8(+) cytotoxic t lymphocytes (ctl) can rapidly kill beta-cells and therefore contribute to the development of type 1 diabetes (t1d). ctl-mediated beta-cell killing can occur via perforin-mediated lysis, fas-fas-l interaction, and the secretion of tnf-alpha or ifn-gamma. the secretion of ifn-gamma can contribute to beta-cell death directly by eliciting nitric oxide production, and indirectly by upregulating mhc class i and 'unmasking' beta-cells for recognition by ctl. earlier studies in the ri ... | 2006 | 17045460 |
| lcmv transmission by organ transplantation. | | 2006 | 17050901 |
| lcmv transmission by organ transplantation. | | 2006 | 17054324 |
| immunoproteasomes are essential for clearance of listeria monocytogenes in nonlymphoid tissues but not for induction of bacteria-specific cd8+ t cells. | microbial infections induce the replacement of constitutive proteasomes by immunoproteasomes (i-proteasomes). i-proteasomes support efficient generation of mhc class i epitopes and influence immunodominance hierarchies of cd8(+) t cells. recently, the function of i-proteasomes in antimicrobial responses was challenged by showing that the lack of i-proteasomes has no effect on induction and function of lymphocytic choriomeningitis virus-specific cd8(+) t cells. here, we show that infection with l ... | 2006 | 17056553 |
| the price of the cd27-cd70 costimulatory axis: you can't have it all. | t cells require costimulatory signals for optimal proliferation, differentiation, and survival and thus to induce protective immune responses. recent data, however, show that during chronic lymphocyte choriomeningitis virus (lcmv) infection, triggering of the costimulatory receptor cd27 by its ligand cd70 impedes neutralizing antibody production and leads to viral persistence. thus, while being crucial for the induction of some adaptive effector pathways, costimulation may block the development ... | 2006 | 17060478 |
| high prevalence of antibodies to lymphocytic choriomeningitis virus in a murine typhus endemic region in croatia. | a retrospective serological survey was carried out by the indirect immunofluorescence assay (ifa) and complement fixation (cf) test in a sample of 425 healthy residents (240 females and 185 males) to investigate whether lymphocytic choriomeningitis virus (lcmv) circulates in the rural area of the northern croatian island of vir, which is known to be endemic for murine typhus. the overall prevalence of lcmv antibodies detected by ifa was found to be 36% (155 out of 425) and 13% (54 out of 425) by ... | 2006 | 17063527 |
| [analysis of in vitro delivering cd8+ t epitopes by attenuated bacteria]. | to analyze the efficiency of delivery for cd8(+) t cell epitopes by recombinant bacteria vectors. | 2006 | 17077012 |
| 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 |
| quantification of repertoire diversity of influenza-specific epitopes with predominant public or private tcr usage. | the h-2db-restricted cd8 t cell immune response to influenza a is directed at two well-described epitopes, nucleoprotein 366 (np366) and acid polymerase 224 (pa224). the responses to the two epitopes are very different. the epitope np366-specific response is dominated by tcr clonotypes that are public (shared by most mice), whereas the epitope pa224-specific response is private (unique within each infected animal). in addition to being public, the np366-specific response is dominated by a few cl ... | 2006 | 17082583 |
| the role of myristoylation in the membrane association of the lassa virus matrix protein z. | the z protein is the matrix protein of arenaviruses and has been identified as the main driving force for budding. both lcmv and lassa virus z proteins bud from cells in the absence of other viral proteins as enveloped virus-like particles. z accumulates near the inner surface of the plasma membrane where budding takes place. furthermore, biochemical data have shown that z is strongly membrane associated. the primary sequence of z lacks a typical transmembrane domain and until now it is not unde ... | 2006 | 17083745 |
| virus scores a perfect 10. | | 2006 | 17088891 |
| 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 |
| parameters governing exhaustion of rare t cell-independent neutralizing igm-producing b cells after lcmv infection. | the late appearance of neutralizing antibodies (nab) against lymphocytic choriomeningitis virus (lcmv) has been attributed to various factors including immunopathology, low frequency of high-affinity specific b cells and competition by nonspecific polyclonal b cell activation. to investigate the activation of lcmv-nab-producing b cells early following infection, we performed adoptive transfers of lcmv-specific b cells into wt recipients. by modulating parameters such as viral load, number of spe ... | 2006 | 17125146 |
| 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 |
| heat shock up-regulates lmp2 and lmp7 and enhances presentation of immunoproteasome-dependent epitopes. | the heat shock response is a canonical regulatory pathway by which cellular stressors such as heat and oxidative stress alter the expression of stress-responsive genes. some of these stress-responsive genes (heat shock proteins and mhc class i (mhc i)-related chains) play a significant role in the immune system. in this study, we have investigated the impact of stimulating the heat shock response on genes involved in the mhc i presentation pathway. we report that two inducible subunits of the pr ... | 2006 | 17142736 |
| 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 |
| active antiviral t-lymphocyte response can be redirected against tumor cells by antitumor antibody x mhc/viral peptide conjugates. | to redirect an ongoing antiviral t-cell response against tumor cells in vivo, we evaluated conjugates consisting of antitumor antibody fragments coupled to class i mhc molecules loaded with immunodominant viral peptides. | 2006 | 17189415 |
| 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 |