| epigenetic manipulation restores functions of defective cd8(+) t cells from chronic viral infection. | functional exhaustion of antigen-specific t cells is a defining characteristic of many chronic infections, but the underlying mechanisms of t cell dysfunction are not well understood. epigenetics plays an important role in the control of t cell development, differentiation, and function. to examine if epigenetics also plays a role in t cell exhaustion, we analyzed chromatin remodeling in cd8(+) t cells from mice with chronic lymphocytic choriomeningitis virus infection. we observed downregulatio ... | 2014 | 28153206 |
| in vivo rna interference screens identify regulators of antiviral cd4(+) and cd8(+) t cell differentiation. | classical genetic approaches to examine the requirements of genes for t cell differentiation during infection are time consuming. here we developed a pooled approach to screen 30-100+ genes individually in separate antigen-specific t cells during infection using short hairpin rnas in a microrna context (shrnamir). independent screens using t cell receptor (tcr)-transgenic cd4(+) and cd8(+) t cells responding to lymphocytic choriomeningitis virus (lcmv) identified multiple genes that regulated de ... | 2014 | 25148027 |
| differences in the transduction of canonical wnt signals demarcate effector and memory cd8 t cells with distinct recall proliferation capacity. | protection against reinfection is mediated by ag-specific memory cd8 t cells, which display stem cell-like function. because canonical wnt (wingless/int1) signals critically regulate renewal versus differentiation of adult stem cells, we evaluated wnt signal transduction in cd8 t cells during an immune response to acute infection with lymphocytic choriomeningitis virus. whereas naive cd8 t cells efficiently transduced wnt signals, at the peak of the primary response to infection only a fraction ... | 2014 | 25127860 |
| interplay between regulatory t cells and pd-1 in modulating t cell exhaustion and viral control during chronic lcmv infection. | regulatory t (t reg) cells are critical for preventing autoimmunity mediated by self-reactive t cells, but their role in modulating immune responses during chronic viral infection is not well defined. to address this question and to investigate a role for t reg cells in exhaustion of virus-specific cd8 t cells, we depleted t reg cells in mice chronically infected with lymphocytic choriomeningitis virus (lcmv). t reg cell ablation resulted in 10-100-fold expansion of functional lcmv-specific cd8 ... | 2014 | 25113973 |
| mhc basis of t cell-dependent heterologous immunity to arenaviruses. | having a history of infection with one pathogen may sometimes provide a level of t cell-dependent protective heterologous immunity to another pathogen. this immunity was initially thought due to cross-reactive t cell epitopes, but recent work has suggested that such protective immunity can be initiated nonspecifically by the action of cytokines on memory t cells. we retested this concept using two small and well-defined arenaviruses, lymphocytic choriomeningitis virus (lcmv) and pichinde virus ( ... | 2014 | 25094042 |
| [meningitis after a mouse bite]. | infection with the lymphocytic choriomeningitis virus is a human zoonosis caused by a rodent-borne arenavirus and is often seen in autumn and winter when mice retreat into houses. infection in humans is acquired after inhalation of aerosols or direct contact with excreta of an infected rodent. | 2014 | 25017980 |
| chronic viral infection promotes sustained th1-derived immunoregulatory il-10 via blimp-1. | during the course of many chronic viral infections, the antiviral t cell response becomes attenuated through a process that is regulated in part by the host. while elevated expression of the immunosuppressive cytokine il-10 is involved in the suppression of viral-specific t cell responses, the relevant cellular sources of il-10, as well as the pathways responsible for il-10 induction, remain unclear. in this study, we traced il-10 production over the course of chronic lymphocytic choriomeningiti ... | 2014 | 25003188 |
| the regulatory t cell effector molecule fibrinogen-like protein 2 is necessary for the development of rapamycin-induced tolerance to fully mhc-mismatched murine cardiac allografts. | therapies that promote tolerance in solid organ transplantation will improve patient outcomes by eliminating the need for long-term immunosuppression. to investigate mechanisms of rapamycin-induced tolerance, c3h/hej mice were heterotopically transplanted with mhc-mismatched hearts from balb/cj mice and were monitored for rejection after a short course of rapamycin treatment. mice that had received rapamycin developed tolerance with indefinite graft survival, whereas untreated mice all rejected ... | 2015 | 24990517 |
| conventional but not plasmacytoid dendritic cells foster the systemic virus-induced type i ifn response needed for efficient cd8 t cell priming. | plasmacytoid dendritic cells (pdcs) are considered to be the principal type-i ifn (ifn-i) source in response to viruses, whereas the contribution of conventional dcs (cdcs) has been underestimated because, on a per-cell basis, they are not considered professional ifn-i-producing cells. we have investigated their respective roles in the ifn-i response required for ctl activation. using a nonreplicative virus, baculovirus, we show that despite the high ifn-i-producing abilities of pdcs, in vivo cd ... | 2014 | 24973449 |
| spleen-derived macrophages are readily polarized into classically activated (m1) or alternatively activated (m2) states. | bone marrow derived macrophages (bm-mφ) that differentiate from precursor cells can be polarized into classically activated pro-inflammatory (m1) or alternatively activated (m2) states depending upon the cytokine microenvironment. we questioned whether tissue mφ, such as spleen-derived mφ (sp-mφ), have the ability to differentiate into m1 or m2 cells. we show in response to activation with ifn-gamma (ifn-γ) and lipopolysaccharide (lps), that the sp-mφ readily acquired an m1 status indicated by u ... | 2014 | 24954891 |
| regulation of tissue-dependent differences in cd8+ t cell apoptosis during viral infection. | virus-specific cd8+ t cells in the lymphoid organs contract at the resolution of virus infections by apoptosis or by dissemination into peripheral tissues, and those residing in nonlymphoid organs, including the peritoneal cavity and fat pads, are more resistant to apoptosis than those in the spleen and lymph nodes. this stability of memory t cells in the nonlymphoid tissues may enhance protection to secondary challenges. here, we show that lymphocytic choriomeningitis virus (lcmv)-specific cd8+ ... | 2014 | 24942579 |
| acute and chronic b cell depletion disrupts cd4+ and cd8+ t cell homeostasis and expansion during acute viral infection in mice. | b cells provide humoral protection against pathogens and promote cellular immunity through diverse nonclassical effector functions. to assess b cell function in promoting t cell homeostasis, mature b cells were either acutely or chronically depleted in mice using cd20 mab. acute b cell depletion in either 2- or 4-mo-old mice significantly reduced spleen and lymph node cd4(+) and cd8(+) t cell numbers, including naive, activated, and foxp3(+)cd25(+)cd4(+) regulatory t cell subsets. the numbers of ... | 2014 | 24928986 |
| cell entry of lymphocytic choriomeningitis virus is restricted in myotubes. | in mice persistently infected since birth with the prototypic arenavirus lymphocytic choriomeningitis viurs, viral antigen and rna are readily detected in most organs and cell types but remarkably absent in skeletal muscle. here we report that mouse c2c12 myoblasts that are readily infected by lcmv, become highly refractory to lcmv infection upon their differentiation into myotubes. myotube's resistance to lcmv was not due to an intracellular restriction of virus replication but rather an impair ... | 2014 | 24928036 |
| structure of the lcmv nucleoprotein provides a template for understanding arenavirus replication and immunosuppression. | the x-ray crystal structure of the lymphocytic choriomeningitis virus nucleoprotein c-terminal immunosuppressive domain (lcmv npδ340) was determined to 2.0 å resolution. the structure indicates that lcmv npδ340, like the other structurally characterized arenaviral nucleoproteins, adopts the fold of an exonuclease. this structure provides a crucial three-dimensional template for functional exploration of the replication and immunosuppression of this prototypic arenavirus. | 2014 | 24914986 |
| loss of the death receptor cd95 (fas) expression by dendritic cells protects from a chronic viral infection. | chronic viral infections incapacitate adaptive immune responses by "exhausting" virus-specific t cells, inducing their deletion and reducing productive t-cell memory. viral infection rapidly induces death receptor cd95 (fas) expression by dendritic cells (dcs), making them susceptible to elimination by the immune response. lymphocytic choriomeningitis virus (lcmv) clone 13, which normally establishes a chronic infection, is rapidly cleared in c57black6/j mice with conditional deletion of fas in ... | 2014 | 24912151 |
| costimulatory tnfr family members in control of viral infection: outstanding questions. | members of the tnfr family can play prominent roles in controlling the magnitude, duration and phenotype of the immune response to viruses. the importance of particular tnfrs in different viral infections and whether they contribute to viral control or pathology is dependent on the virus and the severity of the infection. tnfrs and their ligands are widely and differentially expressed on both adaptive and innate immune cell types. the cell types through which tnfrs exert their effects, the uniqu ... | 2014 | 24910294 |
| type i interferons protect t cells against nk cell attack mediated by the activating receptor ncr1. | direct type i interferon (ifn) signaling on t cells is necessary for the proper expansion, differentiation, and survival of responding t cells following infection with viruses prominently inducing type i ifn. the reasons for the abortive response of t cells lacking the type i ifn receptor (ifnar1(-/-)) remain unclear. we report here that ifnar1(-/-) t cells were highly susceptible to natural killer (nk) cell-mediated killing in a perforin-dependent manner. depletion of nk cells prior to lymphocy ... | 2014 | 24909889 |
| type i interferon protects antiviral cd8+ t cells from nk cell cytotoxicity. | despite development of new antiviral drugs, viral infections are still a major health problem. the most potent antiviral defense mechanism is the innate production of type i interferon (ifn-i), which not only limits virus replication but also promotes antiviral t cell immunity through mechanisms, which remain insufficiently studied. using the murine lymphocytic choriomeningitis virus model system, we show here that ifn-i signaling on t cells prevented their rapid elimination in vivo. microarray ... | 2014 | 24909887 |
| type i interferon is a therapeutic target for virus-induced lethal vascular damage. | the outcome of a viral infection reflects the balance between virus virulence and host susceptibility. the clone 13 (cl13) variant of lymphocytic choriomeningitis virus--a prototype of old world arenaviruses closely related to lassa fever virus--elicits in c57bl/6 and balb/c mice abundant negative immunoregulatory molecules, associated with t-cell exhaustion, negligible t-cell-mediated injury, and high virus titers that persist. conversely, here we report that in nzb mice, despite the efficient ... | 2014 | 24889626 |
| epigenetic manipulation restores functions of defective cd8⁺ t cells from chronic viral infection. | functional exhaustion of antigen-specific t cells is a defining characteristic of many chronic infections, but the underlying mechanisms of t cell dysfunction are not well understood. epigenetics plays an important role in the control of t cell development, differentiation, and function. to examine if epigenetics also plays a role in t cell exhaustion, we analyzed chromatin remodeling in cd8(+) t cells from mice with chronic lymphocytic choriomeningitis virus infection. we observed downregulatio ... | 2014 | 24861055 |
| notes from the field: a cluster of lymphocytic choriomeningitis virus infections transmitted through organ transplantation-iowa, 2013. | | 2014 | 24854024 |
| re-engineering vesicular stomatitis virus to abrogate neurotoxicity, circumvent humoral immunity, and enhance oncolytic potency. | as cancer treatment tools, oncolytic viruses (ov) have yet to realize what some see as their ultimate clinical potential. in this study, we have engineered a chimeric vesicular stomatitis virus (vsv) that is devoid of its natural neurotoxicity while retaining potent oncolytic activity. the envelope glycoprotein (g) of vsv was replaced with a variant glycoprotein of the lymphocytic choriomeningitis virus (lcmv-gp), creating a replicating therapeutic, rvsv(gp), that is benign in normal brain but c ... | 2014 | 24812275 |
| congenitally acquired persistent lymphocytic choriomeningitis viral infection reduces neuronal progenitor pools in the adult hippocampus and subventricular zone. | lymphocytic choriomeningitis virus (lcmv) can be transmitted through congenital infection, leading to persistent infection of numerous organ systems including the central nervous system (cns). adult mice persistently infected with lcmv (lcmv-cgpi mice) exhibit learning deficits, such as poor performance in spatial discrimination tests. given that deficits in spatial learning have been linked to defects in adult neurogenesis, we investigated the impact of congenital lcmv infection on generation o ... | 2014 | 24802239 |
| type i interferon suppresses de novo virus-specific cd4 th1 immunity during an established persistent viral infection. | cd4 t cells are central to orchestrate, sustain, and potentially regenerate antiviral immunity throughout persistent viral infections. although the evolving immune environment during persistent infection reshapes established cd4 t-cell responses, the fate of naïve cd4 t cells primed in the midst of persistent infection is unclear. we demonstrate that, in marked contrast to the onset of infection, virus-specific cd4 t cells primed during an established persistent infection have diminished ability ... | 2014 | 24799699 |
| editorial: not all roads to t cell memory go through stat4 and t-bet. | | 2014 | 27929377 |
| irf7-dependent type i interferon production induces lethal immune-mediated disease in stat1 knockout mice infected with lymphocytic choriomeningitis virus. | following systemic infection with lymphocytic choriomeningitis virus (lcmv), stat1 knockout (ko) mice but not wild-type, stat2 ko, irf9 ko, or ifnar ko mice develop lethal disease perpetrated by cd4(+) t cells. irf7 is a key transcriptional activator of type i ifn (ifn-i) during lcmv infection. here, the role of irf7 in the lethal host response to lcmv infection in stat1 ko mice was examined. in contrast to stat1 ko mice, stat1/irf7 double ko (dko) mice survived lcmv infection with a reduced imm ... | 2014 | 24760883 |
| protracted symptoms in lymphocytic choriomeningitis: a case report. | assumed to be underreported and underrecognized, lymphocytic choriomeningitis presents as a febrile illness transmitted by the common house mouse, mus musculus. although asymptomatic or mild febrile illnesses are commonplace, meningitis and meningoencephalitis may develop after symptoms have seemed to improve. neurologic sequelae are not typical but have been reported and can persist for months. we report a documented case of lymphocytic choriomeningitis in which a previously healthy 17-year-old ... | 2015 | 24736119 |
| type i interferons directly inhibit regulatory t cells to allow optimal antiviral t cell responses during acute lcmv infection. | regulatory t (t reg) cells play an essential role in preventing autoimmunity but can also impair clearance of foreign pathogens. paradoxically, signals known to promote t reg cell function are abundant during infection and could inappropriately enhance t reg cell activity. how t reg cell function is restrained during infection to allow the generation of effective antiviral responses remains largely unclear. we demonstrate that the potent antiviral type i interferons (ifns) directly inhibit co-st ... | 2014 | 24711580 |
| augmented replicative capacity of the boosting antigen improves the protective efficacy of heterologous prime-boost vaccine regimens. | prime-boost immunization regimens have proven efficacious at generating robust immune responses. however, whether the level of replication of the boosting antigen impacts the magnitude and protective efficacy of vaccine-elicited immune responses remains unclear. to evaluate this, we primed mice with replication-defective adenovirus vectors expressing the lymphocytic choriomeningitis virus (lcmv) glycoprotein (gp), followed by boosting with either lcmv armstrong, which is rapidly controlled, or l ... | 2014 | 24648461 |
| notes from the field: a cluster of lymphocytic choriomeningitis virus infections transmitted through organ transplantation - iowa, 2013. | on april 26, 2013, the united network for organ sharing reported to cdc a cluster of ill organ transplant recipients in iowa with a common organ donor. infection with lymphocytic choriomeningitis virus (lcmv) was suspected. lcmv is a rodent-borne virus that most commonly causes nonfatal, influenza-like illness and occasional aseptic meningitis, but when transmitted through organ transplantation or in utero can cause severe, life-threatening disease. | 2014 | 24647402 |
| platelet production proceeds independently of the intrinsic and extrinsic apoptosis pathways. | bh3 mimetic drugs that target bcl-2 family pro-survival proteins to induce tumour cell apoptosis represent a new era in cancer therapy. clinical trials of navitoclax (abt-263, which targets bcl-2, bcl-xl and bcl-w) have shown great promise, but encountered dose-limiting thrombocytopenia. recent work has demonstrated that this is due to the inhibition of bcl-xl, which is essential for platelet survival. these findings raise new questions about the established model of platelet shedding by megakar ... | 2014 | 24632563 |
| transcription factor stat3 and type i interferons are corepressive insulators for differentiation of follicular helper and t helper 1 cells. | follicular helper t (tfh) cells are required for the establishment of t-dependent b cell memory and high affinity antibody-secreting cells. we have revealed herein opposing roles for signal transducer and activator of transcription 3 (stat3) and type i interferon (ifn) signaling in the differentiation of tfh cells following viral infection. stat3-deficient cd4(+) t cells had a profound defect in tfh cell differentiation, accompanied by decreased germinal center (gc) b cells and antigen-specific ... | 2014 | 24631156 |
| the p75 neurotrophin receptor is required for the major loss of sympathetic nerves from islets under autoimmune attack. | our goal was to determine the role of the p75 neurotrophin receptor (p75ntr) in the loss of islet sympathetic nerves that occurs during the autoimmune attack of the islet. the islets of transgenic (tg) mice in which β-cells express a viral glycoprotein (gp) under the control of the insulin promotor (ins2) were stained for neuropeptide y before, during, and after virally induced autoimmune attack of the islet. ins2-gp(tg) mice injected with lymphocytic choriomeningitis virus (lcmv) lost islet sym ... | 2014 | 24608438 |
| sphingosine analog aal-r promotes activation of lcmv-infected dendritic cells. | sphingosine analogs display diverse immunoregulatory activities with curative potential in autoimmune diseases and viral infections. recently, the sphingosine analog aal-r was shown to increase dc activation upon tlr7 stimulation. here, we investigated the effect of aal-r on activation of dendritic cells (dcs) infected by lymphocytic choriomeningitis virus (lcmv). concomitant treatment of lcmv-infected dcs with aal-r enhanced dc maturation and dc ability to stimulate and expand antiviral cd8(+) ... | 2014 | 24605791 |
| intrahepatic innate lymphoid cells secrete il-17a and il-17f that are crucial for t cell priming in viral infection. | intrahepatic cell-derived, early il-17 is important for activating apcs in viral infection; however, the source and regulation of this il-17 surge in the liver microenvironment are not well defined. in this article, we present evidence for a significant expansion of il-17a/f-producing cells in mouse liver within 24 h of adenovirus infection. in addition to γδ t cells, a subset of il-17a/f(+) cells expressed no myeloid or lymphoid lineage markers. instead, they expressed high levels of stem cell ... | 2014 | 24600029 |
| duality of the murine cd8 compartment. | cd8αβ plays crucial roles in the thymic selection, differentiation, and activation of some, but not all, cd8(+) t cells, whereas cd8αα does not. to investigate these roles, we produced mice that expressed transgene p14 t-cell receptor β (tcrβ) chain and cd8β or did not (wt and ko mice, respectively). the primary cd8(+) t-cell response to acute lymphocytic choriomeningitis virus (lcmv) infection was predominantly d(b)/gp33 specific and cd8 independent in ko mice and was mostly cd8 dependent in wt ... | 2014 | 24594598 |
| blimp-1 represses cd8 t cell expression of pd-1 using a feed-forward transcriptional circuit during acute viral infection. | programmed cell death 1 (pd-1) is an inhibitory immune receptor that regulates t cell function, yet the molecular events that control its expression are largely unknown. we show here that b lymphocyte-induced maturation protein 1 (blimp-1)-deficient cd8 t cells fail to repress pd-1 during the early stages of cd8 t cell differentiation after acute infection with lymphocytic choriomeningitis virus (lcmv) strain armstrong. blimp-1 represses pd-1 through a feed-forward repressive circuit by regulati ... | 2014 | 24590765 |
| beta-cell specific production of il6 in conjunction with a mainly intracellular but not mainly surface viral protein causes diabetes. | inflammatory mechanisms play a key role in the pathogenesis of type 1 and type 2 diabetes. il6, a pleiotropic cytokine with impact on immune and non-immune cell types, has been proposed to be involved in the events causing both forms of diabetes and to play a key role in experimental insulin-dependent diabetes development. the aim of this study was to investigate how beta-cell specific overexpression of il-6 influences diabetes development. we developed two lines of rat insulin promoter (rip)-ly ... | 2014 | 24582317 |
| irf4 and batf are critical for cd8⁺ t-cell function following infection with lcmv. | cd8(+) t-cell functions are critical for preventing chronic viral infections by eliminating infected cells. for healthy immune responses, beneficial destruction of infected cells must be balanced against immunopathology resulting from collateral damage to tissues. these processes are regulated by factors controlling cd8(+) t-cell function, which are still incompletely understood. here, we show that the interferon regulatory factor 4 (irf4) and its cooperating binding partner b-cell-activating tr ... | 2014 | 24531538 |
| b cell depletion curtails cd4+ t cell memory and reduces protection against disseminating virus infection. | dynamic interactions between cd4(+) t cells and b cells are needed for humoral immunity and cd4(+) t cell memory. it is not known whether b cells are needed early on to induce the formation of memory precursor cells or are needed later to sustain memory cells. in this study, primary and memory cd4(+) t cells responses were followed in wild-type mice that were depleted of mature b cells by anti-cd20 before or different times after acute lymphocytic choriomeningitis virus infection. the ab treatme ... | 2014 | 24453250 |
| trace-forward investigation of mice in response to lymphocytic choriomeningitis virus outbreak. | during follow-up of a 2012 us outbreak of lymphocytic choriomeningitis virus (lcmv), we conducted a trace-forward investigation. lcmv-infected feeder mice originating from a us rodent breeding facility had been distributed to >500 locations in 21 states. all mice from the facility were euthanized, and no additional persons tested positive for lcmv infection. | 2014 | 24447898 |
| lymphocytic choriomeningitis virus in employees and mice at multipremises feeder-rodent operation, united states, 2012. | we investigated the extent of lymphocytic choriomeningitis virus (lcmv) infection in employees and rodents at 3 commercial breeding facilities. of 97 employees tested, 31 (32%) had igm and/or igg to lcmv, and aseptic meningitis was diagnosed in 4 employees. of 1,820 rodents tested in 1 facility, 382 (21%) mice (mus musculus) had detectable igg, and 13 (0.7%) were positive by reverse transcription pcr; lcmv was isolated from 8. rats (rattus norvegicus) were not found to be infected. s-segment rna ... | 2014 | 24447605 |
| to investigate the necessity of stra6 upregulation in t cells during t cell immune responses. | our earlier study revealed that stra6 (stimulated by retinoic acid gene 6) was up-regulated within 3 h of tcr stimulation. stra6 is the high-affinity receptor for plasma retinol-binding protein (rbp) and mediates cellular vitamin a uptake. we generated stra6 knockout (ko) mice to assess whether such up-regulation was critical for t-cell activation, differentiation and function. stra6 ko mice under vitamin a sufficient conditions were fertile without apparent anomalies upon visual inspection. the ... | 2013 | 24391722 |
| detection of foreign antigen-specific cd4(+)foxp3(+) regulatory t cells by mhc class ii tetramer and intracellular cd154 staining. | the unrestricted population of cd4(+)foxp3(+) regulatory t (treg) cells, which have been known to control the expression of autoimmune diseases and protective immunity to inflammatory reactions, has led to greater appreciation of functional plasticity. detecting and/or isolating ag-specific cd4(+)foxp3(+) tregs at the single cell level are required to study their function and plasticity. in this study, we established and compared both mhc class ii tetramer and intracellular cd154 staining, in or ... | 2013 | 24385945 |
| intravascular staining for discrimination of vascular and tissue leukocytes. | characterization of the cellular participants in tissue immune responses is crucial to understanding infection, cancer, autoimmunity, allergy, graft rejection and other immunological processes. previous reports indicate that leukocytes in lung vasculature fail to be completely removed by perfusion. several studies suggest that intravascular staining may discriminate between tissue-localized and blood-borne cells in the mouse lung. here we outline a protocol for the validation and use of intravas ... | 2014 | 24385150 |
| graded defects in cytotoxicity determine severity of hemophagocytic lymphohistiocytosis in humans and mice. | primary hemophagocytic lymphohistiocytosis (hlh) is a life-threatening disease of hyperinflammation resulting from immune dysregulation due to inherited defects in the cytolytic machinery of natural killer and t cells. in humans, mutations in seven genes encoding proteins involved in cytolytic effector functions have so far been identified that predispose to hlh. however, although most affected patients develop hlh eventually, disease onset and severity are highly variable. due to the genetic he ... | 2013 | 24379813 |
| functional limitations of plasmacytoid dendritic cells limit type i interferon, t cell responses and virus control in early life. | infant mortality from viral infection remains a major global health concern: viruses causing acute infections in immunologically mature hosts often follow a more severe course in early life, with prolonged or persistent viral replication. similarly, the we strain of lymphocytic choriomeningitis virus (lcmv-we) causes acute self-limiting infection in adult mice but follows a protracted course in infant animals, in which lcmv-specific cd8⁺ t cells fail to expand and control infection. by disruptin ... | 2013 | 24376875 |
| inhibitors of apoptosis proteins (iaps) are required for effective t-cell expansion/survival during antiviral immunity in mice. | inhibitors of apoptosis proteins (iaps) were originally described as regulating apoptosis by direct binding to caspases. more recently, iaps have been identified as important modulators of canonical and noncanonical nuclear factor κb signaling via their ubiquitin-e3 ligase activity. iaps are therefore, not only gatekeepers of cell death, but are probably also involved in the regulation of inflammation, as well as innate and adaptive immunity. in this study, we analyzed the role of iaps in t-cell ... | 2014 | 24335231 |
| immunotherapy with tcr-redirected t cells: comparison of tcr-transduced and tcr-engineered hematopoietic stem cell-derived t cells. | redirecting ag specificity by transfer of tcr genes into pbls is an attractive method to generate large numbers of cytotoxic t cells for immunotherapy of cancer and viral diseases. however, transferred tcr chains can pair with endogenous tcr chains, resulting in the formation of mispaired tcr dimers and decreased or unspecific reactivity. tcr gene transfer into hematopoietic stem cells (hscs) is an alternative to create t cells with desired ag specificity, because in this case expression of endo ... | 2014 | 24293634 |
| a newborn with hydrops, hydrocephalus, and ophthalmologic abnormalities. | | 2013 | 26619503 |
| etoposide selectively ablates activated t cells to control the immunoregulatory disorder hemophagocytic lymphohistiocytosis. | hemophagocytic lymphohistiocytosis (hlh) is an inborn disorder of immune regulation caused by mutations affecting perforin-dependent cytotoxicity. defects in this pathway impair negative feedback between cytotoxic lymphocytes and apcs, leading to prolonged and pathologic activation of t cells. etoposide, a widely used chemotherapeutic drug that inhibits topoisomerase ii, is the mainstay of treatment for hlh, although its therapeutic mechanism remains unknown. we used a murine model of hlh, invol ... | 2014 | 24259502 |
| macrophage and t cell produced il-10 promotes viral chronicity. | chronic viral infections lead to cd8(+) t cell exhaustion, characterized by impaired cytokine secretion. presence of the immune-regulatory cytokine il-10 promotes chronicity of lymphocytic choriomeningitis virus (lcmv) clone 13 infection, while absence of il-10/il-10r signaling early during infection results in viral clearance and higher percentages and numbers of antiviral, cytokine producing t cells. il-10 is produced by several cell types during lcmv infection but it is currently unclear whic ... | 2013 | 24244162 |
| virus-specific cd4 and cd8 t cell responses in the absence of th1-associated transcription factors. | effector and memory cd4 and cd8 t cell responses are critical for the control of many intracellular pathogens. the development of these populations is governed by transcription factors that molecularly control their differentiation, function, and maintenance. two transcription factors known to be involved in these processes are tbet and stat4. although tbet has been shown to regulate cd8 t cell fate decisions and effector cd4 t cell choices, the contribution of stat4 is less well understood. to ... | 2014 | 24231259 |
| deletion of naïve t cells recognizing the minor histocompatibility antigen hy with toxin-coupled peptide-mhc class i tetramers inhibits cognate ctl responses and alters immunodominance. | alloreactive t-cell responses directed against minor histocompatibility (h) antigens, which arise from diverse genetic disparities between donor and recipient outside the mhc, are an important cause of rejection of mhc-matched grafts. because clinically significant responses appear to be directed at only a few antigens, the selective deletion of naïve t cells recognizing donor-specific, immunodominant minor h antigens in recipients before transplantation may be a useful tolerogenic strategy. we ... | 2013 | 24161680 |
| targeted deletion of fgl2 leads to increased early viral replication and enhanced adaptive immunity in a murine model of acute viral hepatitis caused by lcmv we. | mounting effective innate and adaptive immune responses are critical for viral clearance and the generation of long lasting immunity. it is known that production of inhibitory factors may result in the inability of the host to clear viruses, resulting in chronic viral persistence. fibrinogen-like protein 2 (fgl2) has been identified as a novel effector molecule of cd4(+)cd25(+) foxp3(+) regulatory t (treg) cells that inhibits immune activity by binding to fcγriib expressed primarily on antigen p ... | 2013 | 24146739 |
| differential t cell responses to residual viral antigen prolong cd4+ t cell contraction following the resolution of infection. | the contraction phase of the t cell response is a poorly understood period after the resolution of infection when virus-specific effector cells decline in number and memory cells emerge with increased frequencies. cd8(+) t cells plummet in number and quickly reach stable levels of memory following acute lymphocytic choriomeningitis virus infection in mice. in contrast, virus-specific cd4(+) t cells gradually decrease in number and reach homeostatic levels only after many weeks. in this study, we ... | 2013 | 24146043 |
| disparate epitopes mediating protective heterologous immunity to unrelated viruses share peptide-mhc structural features recognized by cross-reactive t cells. | closely related peptide epitopes can be recognized by the same t cells and contribute to the immune response against pathogens encoding those epitopes, but sometimes cross-reactive epitopes share little homology. the degree of structural homology required for such disparate ligands to be recognized by cross-reactive tcrs remains unclear. in this study, we examined the mechanistic basis for cross-reactive t cell responses between epitopes from unrelated and pathogenic viruses, lymphocytic choriom ... | 2013 | 24127554 |
| differentiation of antigen-specific t cells with limited functional capacity during mycobacterium tuberculosis infection. | despite the generation of mycobacterium tuberculosis-specific t cell immune responses during the course of infection, only 5 to 10% of exposed individuals develop active disease, while others develop a latent infection. this phenomenon suggests defective m. tuberculosis-specific immunity, which necessitates more careful characterization of m. tuberculosis-specific t cell responses. here, we longitudinally analyzed the phenotypes and functions of m. tuberculosis-specific t cells. in contrast to t ... | 2014 | 24126533 |
| exogenous ox40 stimulation during lymphocytic choriomeningitis virus infection impairs follicular th cell differentiation and diverts cd4 t cells into the effector lineage by upregulating blimp-1. | t cell costimulation is a key component of adaptive immunity to viral infection but has also been associated with pathology because of excessive or altered t cell activity. we recently demonstrated that the tnfr family costimulatory molecule ox40 (cd134) is critically required to sustain antiviral t cell and ab responses that enable control of viral replication in the context of chronic lymphocytic choriomeningitis virus (lcmv) infection. in this study, we investigated whether reinforcing ox40 s ... | 2013 | 24101548 |
| monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses. | because immune responses simultaneously defend and injure the host, the immune system must be finely regulated to ensure the host's survival. here, we have shown that when injected with high toll-like receptor ligand doses or infected with lymphocytic choriomeningitis virus (lcmv) clone 13, which has a high viral turnover, inflammatory monocyte-derived dendritic cells (mo-dcs) engulfed apoptotic erythroid cells. in this process, called hemophagocytosis, phosphatidylserine (ps) served as an "eat- ... | 2013 | 24035363 |
| a cell-intrinsic requirement for nf-κb-inducing kinase in cd4 and cd8 t cell memory. | nf-κb-inducing kinase [(nik), map3k14] is an essential kinase linking a subset of tnfr family members to the noncanonical nf-κb pathway. to assess the cell-intrinsic role of nik in murine t cell function, we generated mixed bone marrow chimeras using bone marrow from nik knockout (ko) and wild-type (wt) donor mice and infected the chimeras with lymphocytic choriomeningitis virus (lcmv). the chimeras possess an apparently normal immune system, including a mixture of nik ko and wt t cells, and the ... | 2013 | 24006459 |
| cell-intrinsic il-27 and gp130 cytokine receptor signaling regulates virus-specific cd4⁺ t cell responses and viral control during chronic infection. | the outcome of chronic viral infections, which affect millions of people worldwide, is greatly dependent on cd4⁺ t cells. here we showed that t cell-specific ablation of the common interleukin-6 (il-6) family receptor, gp130, profoundly compromised virus-specific cd4⁺ t cell survival, t follicular helper responses, and il-21 production at late stages of chronic lymphocytic choriomeningitis virus (lcmv) infection. these effects were cell intrinsic for cd4⁺ t cells and were accompanied by a reduct ... | 2013 | 23993651 |
| global dna methylation remodeling accompanies cd8 t cell effector function. | the differentiation of cd8 t cells in response to acute infection results in the acquisition of hallmark phenotypic effector functions; however, the epigenetic mechanisms that program this differentiation process on a genome-wide scale are largely unknown. in this article, we report the dna methylomes of ag-specific naive and day-8 effector cd8 t cells following acute lymphocytic choriomeningitis virus infection. during effector cd8 t cell differentiation, dna methylation was remodeled such that ... | 2013 | 23956425 |
| the great balancing act: regulation and fate of antiviral t-cell interactions. | the fate of t lymphocytes revolves around a continuous stream of interactions between the t-cell receptor (tcr) and peptide-major histocompatibility complex (mhc) molecules. beginning in the thymus and continuing into the periphery, these interactions, refined by accessory molecules, direct the expansion, differentiation, and function of t-cell subsets. the cellular context of t-cell engagement with antigen-presenting cells, either in lymphoid or non-lymphoid tissues, plays an important role in ... | 2013 | 23947351 |
| diverging role for coronin 1 in antiviral cd4+ and cd8+ t cell responses. | coronin 1 is a member of the evolutionary conserved wd repeat protein family and is highly expressed in hematopoietic cells. coronin 1 is essential for ca(2+) mobilization upon t cell receptor (tcr) stimulation providing a pro-survival signal for naïve peripheral t cells. both in mouse and in human, coronin 1 deficiency is associated with severe t cell lymphopenia. in this work, we have analyzed antiviral t cell-mediated immunity in the presence and absence of coronin 1 in vivo after infection w ... | 2013 | 23933558 |
| promotion and prevention of autoimmune disease by cd8+ t cells. | until recently, little was known about the importance of cd8+ t effectors in promoting and preventing autoimmune disease development. cd8+ t cells can oppose or promote autoimmune disease through activities as suppressor cells and as cytotoxic effectors. studies in several distinct autoimmune models and data from patient samples are beginning to establish the importance of cd8+ t cells in these diseases and to define the mechanisms by which these cells influence autoimmunity. cd8+ effectors can ... | 2013 | 23871638 |
| signal transducer and activator of transcription 3 (stat3) mutations underlying autosomal dominant hyper-ige syndrome impair human cd8(+) t-cell memory formation and function. | the capacity of cd8(+) t cells to control infections and mediate antitumor immunity requires the development and survival of effector and memory cells. il-21 has emerged as a potent inducer of cd8(+) t-cell effector function and memory development in mouse models of infectious disease. however, the role of il-21 and associated signaling pathways in protective cd8(+) t-cell immunity in human subjects is unknown. | 2013 | 23830147 |
| the clinical and immunological significance of gad-specific autoantibody and t-cell responses in type 1 diabetes. | antigen-specific interventions are desirable approaches in type 1 diabetes (t1d) as they can alter islet-specific autoimmunity without systemic side effects. glutamic acid decarboxylase of 65 kda (gad65) is a major autoantigen in type 1 diabetes (t1d) and gad-specific autoimmunity is a common feature of t1d in humans but also in mouse models of the disease. in humans, administration of the gad65 protein in an alum formulation has been shown to reduce c-peptide decline in recently diagnosed patie ... | 2013 | 23770292 |
| nucleoprotein-specific nonneutralizing antibodies speed up lcmv elimination independently of complement and fcγr. | cd8(+) t cells have an essential role in controlling lymphocytic choriomeningitis virus (lcmv) infection in mice. here, we examined the contribution of humoral immunity, including nonneutralizing antibodies (abs), in this infection induced by low virus inoculation doses. mice with impaired humoral immunity readily terminated infection with the slowly replicating lcmv strain armstrong but showed delayed virus elimination after inoculation with the faster replicating lcmv strain we and failed to c ... | 2013 | 23749409 |
| non-neutralizing antibodies protect from chronic lcmv infection independently of activating fcγr or complement. | chronic viral infections lead to cd8(+) t cell exhaustion, characterized by impaired cytokine secretion. the presence of the immune-regulatory cytokine il-10 promotes chronic lymphocytic choriomeningitis virus (lcmv) clone 13 infection in mice, whereas the absence of il-10/il-10r signaling early during infection results in viral clearance and higher percentages and numbers of antiviral, cytokine-producing t cells. however, it is currently unclear which cell populations and effector molecules are ... | 2013 | 23749374 |
| inhibition of multiplication of the prototypic arenavirus lcmv by valproic acid. | valproic acid (vpa), a short chain fatty acid commonly used for treatment of neurological disorders, has been shown to inhibit production of infectious progeny of different enveloped viruses including the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv). in this study we have investigated the mechanisms by which vpa inhibits lcmv multiplication in cultured cells. vpa reduced production of infectious lcmv progeny and virus propagation without exerting a major blockage on either vir ... | 2013 | 23735299 |
| cd4 t cell responses in latent and chronic viral infections. | the spectrum of tasks which is fulfilled by cd4 t cells in the setting of viral infections is large, ranging from support of cd8 t cells and humoral immunity to exertion of direct antiviral effector functions. while our knowledge about the differentiation pathways, plasticity, and memory of cd4 t cell responses upon acute infections or immunizations has significantly increased during the past years, much less is still known about cd4 t cell differentiation and their beneficial or pathological fu ... | 2013 | 23717308 |
| thymus-resident memory cd8+ t cells mediate local immunity. | the thymus is a primary lymphoid organ responsible for production and selection of t cells. nonetheless, mature t cells and in particular activated t cells can reenter the thymus. here, we identified memory cd8(+) t cells specific for lymphocytic choriomeningitis virus or vaccinia virus in the thymus of mice long-time after the infection. cd8(+) t cells were mainly located in the thymic medulla, but also in the cortical areas. interestingly, virus-specific memory cd8(+) t cells in the thymus exp ... | 2013 | 23715993 |
| differentiation of cd8 memory t cells depends on foxo1. | the forkhead o transcription factors (foxo) integrate a range of extracellular signals, including growth factor signaling, inflammation, oxidative stress, and nutrient availability, to substantially alter the program of gene expression and modulate cell survival, cell cycle progression, and many yet to be unraveled cell type-specific responses. naive antigen-specific cd8(+) t cells undergo a rapid expansion and arming of effector function within days of pathogen exposure. in addition, by the pea ... | 2013 | 23712431 |
| il-21 restricts virus-driven treg cell expansion in chronic lcmv infection. | foxp3+ regulatory t (treg) cells are essential for the maintenance of immune homeostasis and tolerance. during viral infections, treg cells can limit the immunopathology resulting from excessive inflammation, yet potentially inhibit effective antiviral t cell responses and promote virus persistence. we report here that the fast-replicating lcmv strain docile triggers a massive expansion of the treg population that directly correlates with the size of the virus inoculum and its tendency to establ ... | 2013 | 23696736 |
| pd-l1 blockade synergizes with il-2 therapy in reinvigorating exhausted t cells. | the inhibitory receptor programmed cell death 1 (pd-1) plays a major role in functional exhaustion of t cells during chronic infections and cancer, and recent clinical data suggest that blockade of the pd-1 pathway is an effective immunotherapy in treating certain cancers. thus, it is important to define combinatorial approaches that increase the efficacy of pd-1 blockade. to address this issue, we examined the effect of il-2 and pd-1 ligand 1 (pd-l1) blockade in the mouse model of chronic lymph ... | 2013 | 23676462 |
| congenital lymphocytic choriomeningitis virus: when to consider the diagnosis. | lymphocytic choriomeningitis virus is a rodent-borne arenavirus that can cause congenital infection affecting the developing central nervous system. when the infection occurs during pregnancy, the virus targets the fetal brain and retina, potentially causing ventriculomegaly, hydrocephalus, chorioretinitis, and neurodevelopmental abnormalities. it has been previously suggested that lymphocytic choriomeningitis virus be added to the list of congenital infections currently included in the torch ac ... | 2014 | 23666045 |
| interleukin-21 is a critical cytokine for the generation of virus-specific long-lived plasma cells. | long-lived plasma cells that reside in the bone marrow constitutively produce antibody in the absence of antigen and are the cellular basis of durable humoral immunity. the generation of these long-lived plasma cells depends upon a series of highly orchestrated interactions between antigen-specific cd4 t cells and b cells and the formation of germinal centers (gcs). in this study, we have examined the role of the cytokine interleukin-21 (il-21) in regulating humoral immunity during acute viral i ... | 2013 | 23637417 |
| interferons lambda, new cytokines with antiviral activity. | interferons (ifns) are key cytokines in the establishment of a multifaceted antiviral response. three distinct types of ifns are now recognized (type i, type ii, and type iii) based on their receptor usage, structural features and biological activities. although all ifns are important mediators of antiviral protection, their roles in antiviral defence vary. interferon lambda (ifn-λ) is a recently discovered group of small helical cytokines capable of inducing an antiviral response both in vitro ... | 2013 | 23600875 |
| lymphocytic choriomeningitis virus: invisible but not innocent. | lymphocytic choriomeningitis virus (lcmv) attracts significant attention both as an important experimental model system to study acute and persistent viral infections, and as a neglected human pathogen of clinical significance. this review focuses on the basic aspects and recent advances in the molecular and cell biology of lcmv, the outcome of lcmv infection on its natural host with an emphasis on persistent infection and the outcome of lcmv infection in humans. lastly, we summarize our contrib ... | 2013 | 23600874 |
| a myriad of functions and complex regulation of the ccr7/ccl19/ccl21 chemokine axis in the adaptive immune system. | the chemokine receptor ccr7 and its ligands ccl19 and ccl21 control a diverse array of migratory events in adaptive immune function. most prominently, ccr7 promotes homing of t cells and dcs to t cell areas of lymphoid tissues where t cell priming occurs. however, ccr7 and its ligands also contribute to a multitude of adaptive immune functions including thymocyte development, secondary lymphoid organogenesis, high affinity antibody responses, regulatory and memory t cell function, and lymphocyte ... | 2013 | 23587803 |
| distinct memory cd4+ t cells with commitment to t follicular helper- and t helper 1-cell lineages are generated after acute viral infection. | cd4(+) t follicular helper (tfh) cells provide the required signals to b cells for germinal center reactions that are necessary for long-lived antibody responses. however, it remains unclear whether there are cd4(+) memory t cells committed to the tfh cell lineage after antigen clearance. by using adoptive transfer of antigen-specific memory cd4(+) t cell subpopulations in the lymphocytic choriomeningitis virus infection model, we found that there are distinct memory cd4(+) t cell populations wi ... | 2013 | 23583644 |
| persistent lcmv infection is controlled by blockade of type i interferon signaling. | during persistent viral infections, chronic immune activation, negative immune regulator expression, an elevated interferon signature, and lymphoid tissue destruction correlate with disease progression. we demonstrated that blockade of type i interferon (ifn-i) signaling using an ifn-i receptor neutralizing antibody reduced immune system activation, decreased expression of negative immune regulatory molecules, and restored lymphoid architecture in mice persistently infected with lymphocytic chor ... | 2013 | 23580529 |
| blockade of chronic type i interferon signaling to control persistent lcmv infection. | type i interferons (ifn-i) are critical for antiviral immunity; however, chronic ifn-i signaling is associated with hyperimmune activation and disease progression in persistent infections. we demonstrated in mice that blockade of ifn-i signaling diminished chronic immune activation and immune suppression, restored lymphoid tissue architecture, and increased immune parameters associated with control of virus replication, ultimately facilitating clearance of the persistent infection. the accelerat ... | 2013 | 23580528 |
| cd4(+) t-cell inhibitory ligands: a tool for characterizing dysfunctional cd4(+) t cells during chronic infection. | activation of cd4(+) t cells helps to establish and maintain immune responses. during infection with lymphocytic choriomeningitis virus (lcmv) clone 13, the cd4(+) t-cell responses are lost. in this study, we were interested in the nature of the cd4(+) t-cell responses following infection with lcmv clone 13. to pursue this question, we infected c57bl/6 mice with lcmv clone 13. we used a gp66-80 mhc class ii tetramer to determine whether the cd4(+) t cells were present following infection with lc ... | 2013 | 23566283 |
| mcl-1 antagonizes bax/bak to promote effector cd4(+) and cd8(+) t-cell responses. | members of the bcl-2 family have critical roles in regulating tissue homeostasis by modulating apoptosis. anti-apoptotic molecules physically interact and restrain pro-apoptotic family members preventing the induction of cell death. however, the specificity of the functional interactions between pro- and anti-apoptotic bcl-2 family members remains unclear. the pro-apoptotic bcl-2 family member bcl-2 interacting mediator of death (bim) has a critical role in promoting the death of activated, effe ... | 2013 | 23558951 |
| epidemiological and phylogenetic analysis of institutional mouse parvoviruses. | mouse parvoviruses (mpvs) are small, single-stranded, 5 kb dna viruses that are subclinical and endemic in many laboratory mouse colonies. mpvs cause more distinctive deleterious effects in immune-compromised or genetically-engineered mice than immuno-competent mice. at the university of louisville (u of l), there was an unexpected increase of mpv sero-positivity for mpv infections in mouse colonies between january 2006 and february 2007, resulting in strategic husbandry changes aimed at control ... | 2013 | 23545399 |
| cooperativity between cd8+ t cells, non-neutralizing antibodies, and alveolar macrophages is important for heterosubtypic influenza virus immunity. | seasonal epidemics of influenza virus result in ∼36,000 deaths annually in the united states. current vaccines against influenza virus elicit an antibody response specific for the envelope glycoproteins. however, high mutation rates result in the emergence of new viral serotypes, which elude neutralization by preexisting antibodies. t lymphocytes have been reported to be capable of mediating heterosubtypic protection through recognition of internal, more conserved, influenza virus proteins. here ... | 2013 | 23516357 |
| interferon regulatory factor 7 (irf7) is required for the optimal initial control but not subsequent clearance of lymphocytic choriomeningitis virus infection in mice. | the role of irf7 in the host response to lymphocytic choriomeningitis virus (lcmv) armstrong 53b infection of mice was investigated. intracranial infection of irf7 ko mice was associated with delayed onset of lcm, increased survival and significantly reduced expression of the ifng gene in the brain but not in the periphery. irf7 ko mice showed impaired control of lcmv replication and delayed clearance of lcmv. similar numbers of activated anti-lcmv-gp(33-41) cd8+ t cells were present in the brai ... | 2013 | 23490048 |
| il-21 promotes cd8+ ctl activity via the transcription factor t-bet. | cd8(+) t cells are fundamental for immune-mediated clearance of viral infections and contribute to immune pathology in autoimmune diseases such as type 1 diabetes. to execute these functions, cd8(+) t cells must differentiate into ctls, a process that is precisely regulated by a variety of cytokines, costimulatory molecules, and transcription factors. il-21 is an il-2 family cytokine and a growth factor for multiple lymphocyte effector lineages, including cytotoxic cd8(+) t cells. recent studies ... | 2013 | 23479229 |
| intrinsic defects in cd8 t cells with aging contribute to impaired primary antiviral responses. | aging is associated with altered immune responses, particularly with a diminished cd8 t cell response. although both intrinsic and extrinsic factors are hypothesized to impact this decreased t cell response, the direct evidence of an intrinsic deficiency in virus-specific cd8 t cells is limited. in this study, a tcr transgenic (tg) p14 mouse model was utilized to compare the activation and proliferation of the tg cd8 t cells of young and aged p14 mice upon stimulation with antigen or infection w ... | 2013 | 23473930 |
| lymphocytic choriomeningitis virus infections among american indians. | | 2013 | 23460992 |
| chronic but not acute virus infection induces sustained expansion of myeloid suppressor cell numbers that inhibit viral-specific t cell immunity. | resolution of acute and chronic viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. here we report that infection with acute armstrong (arm) or chronic clone 13 (c13) strains of lymphocytic choriomeningitis virus (lcmv) led to two distinct phases of innate immune response. during the first 72 hr of infection, dendritic cells upregulated activation markers and stimulated antiviral cd8(+) t cells, independent of viral strain. seven days after in ... | 2013 | 23438822 |
| the risk of hemophagocytic lymphohistiocytosis in hermansky-pudlak syndrome type 2. | genetic disorders of lymphocyte cytotoxicity predispose patients to hemophagocytic lymphohistiocytosis (hlh). reduced lymphocyte cytotoxicity has been demonstrated in hermansky-pudlak syndrome type 2 (hps2), but only a single patient was reported who developed hlh. because that patient also carried a potentially contributing heterozygous rab27a mutation, the risk for hlh in hps2 remains unclear. we analyzed susceptibility to hlh in the pearl mouse model of hps2. after infection with lymphocytic ... | 2013 | 23403622 |
| assessment of cd4(+) and cd8 (+) t cell responses using mhc class i and ii tetramers. | the low frequency of t cells specific for given antigens makes the study of antigen-specific t cell responses difficult. the development of mhc class i and ii tetramer staining techniques allows precise quantification and tracking of antigen-specific cd8(+) and cd4(+) t cell responses. here, we describe a protocol for mhc class i and ii tetramer staining of mouse t cells isolated from various tissues of mice infected with lymphocytic choriomeningitis virus (lcmv) or with murine cytomegalovirus ( ... | 2013 | 23397390 |
| blockade but not overexpression of the junctional adhesion molecule c influences virus-induced type 1 diabetes in mice. | type 1 diabetes (t1d) results from the autoimmune destruction of insulin-producing beta-cells in the pancreas. recruitment of inflammatory cells is prerequisite to beta-cell-injury. the junctional adhesion molecule (jam) family proteins jam-b and jam-c are involved in polarized leukocyte transendothelial migration and are expressed by vascular endothelial cells of peripheral tissue and high endothelial venules in lympoid organs. blocking of jam-c efficiently attenuated cerulean-induced pancreati ... | 2013 | 23372751 |
| arenavirus reverse genetics for vaccine development. | arenaviruses are important human pathogens with no food and drug administration (fda)-licensed vaccines available and current antiviral therapy being limited to an off-label use of the nucleoside analogue ribavirin of limited prophylactic efficacy. the development of reverse genetics systems represented a major breakthrough in arenavirus research. however, rescue of recombinant arenaviruses using current reverse genetics systems has been restricted to rodent cells. in this study, we describe the ... | 2013 | 23364194 |
| reversal of chronic to resolved infection by il-10 blockade is lcmv strain dependent. | chronic viral infections lead to cd8(+) t-cell exhaustion, characterized by impaired cytokine secretion. the immune-regulatory cytokine il-10 promotes chronicity of infection with lymphocytic choriomeningitis virus (lcmv) clone 13, as absence of il-10 or blocking of il-10r during early lcmv clone 13 infection results in viral clearance. thus, treatment of humans suffering from chronic viral infections with il-10 neutralizing or il-10r blocking antibodies was proposed to boost virus-specific t-ce ... | 2013 | 23348876 |
| lessons learned and concepts formed from study of the pathogenesis of the two negative-strand viruses lymphocytic choriomeningitis and influenza. | viruses have unique lifestyles. to describe the pathogenesis and significance of viral infection in terms of host responses, resultant injury, and therapy, we focused on two rna viruses: lymphocytic choriomeningitis (lcmv) and influenza (flu). many of the currently established concepts and consequences about viruses and immunologic tolerance, virus-induced immunosuppression, virus-induced autoimmunity, immune complex disease, and virus-lymphocyte and virus-dendritic cell interactions evolved thr ... | 2013 | 23341590 |
| reactive oxygen species delay control of lymphocytic choriomeningitis virus. | cluster of differentiation (cd)8(+) t cells are like a double edged sword during chronic viral infections because they not only promote virus elimination but also induce virus-mediated immunopathology. elevated levels of reactive oxygen species (ros) have been reported during virus infections. however, the role of ros in t-cell-mediated immunopathology remains unclear. here we used the murine lymphocytic choriomeningitis virus to explore the role of ros during the processes of virus elimination ... | 2013 | 23328631 |