| adenovirus e3 mhc inhibitory genes but not tnf/fas apoptotic inhibitory genes expressed in beta cells prevent autoimmune diabetes. | to mimic events and molecules involved in type 1 insulin-dependent diabetes mellitus (t1d), we previously designed a transgenic (tg) mouse model where the viral nucleoprotein (np) gene of lymphocytic choriomeningitis virus (lcmv) was expressed in the thymus to delete high affinity antiself (virus) t cells and in insulin-producing beta cells of the islets of langerhans. such tg mice, termed rip-lcmv, fail to spontaneously develop diabetes. in contrast, when these mice are challenged with lcmv, th ... | 2009 | 19887639 |
| constitutive activation of wnt signaling favors generation of memory cd8 t cells. | t cell factor-1 (tcf-1) and lymphoid enhancer-binding factor 1, the effector transcription factors of the canonical wnt pathway, are known to be critical for normal thymocyte development. however, it is largely unknown if it has a role in regulating mature t cell activation and t cell-mediated immune responses. in this study, we demonstrate that, like il-7ralpha and cd62l, tcf-1 and lymphoid enhancer-binding factor 1 exhibit dynamic expression changes during t cell responses, being highly expres ... | 2010 | 20026746 |
| granzyme b-induced and caspase 3-dependent cleavage of gelsolin by mouse cytotoxic t cells modifies cytoskeleton dynamics. | granule-associated perforin and granzymes (gzms) are key effector molecules of cytotoxic t lymphocytes (tc cells) and natural killer cells and play a critical role in the control of intracellular pathogens and cancer. based on the notion that many gzms, including a, b, c, k, h, and m exhibit cytotoxic activity in vitro, all gzms are believed to serve a similar function in vivo. however, more recent evidence supports the concept that gzms are not unidimensional but, rather, possess non-cytotoxic ... | 2010 | 20395300 |
| serine protease inhibitor 6 protects inkt cells from self-inflicted damage. | the role played by apoptosis in the homeostasis of effector cells of the innate immune system is unclear. serine protease inhibitor 6 (spi6) is an inhibitor of granzyme b (grb) that protects cytotoxic t lymphocytes of the adaptive immune system from apoptosis. to determine whether spi6 also protects cells of the innate immune system from self-inflicted damage we have examined invariant nkt (inkt) cells. spi6-deficient inkt cells harbored increased levels of grb after tcr stimulation with the pbs ... | 2010 | 20543105 |
| il-21 deficiency influences cd8 t cell quality and recall responses following an acute viral infection. | cd4 t cells are principal producers of il-21 and are often required for optimal cd8 t cell responses. therefore, we investigated the importance of il-21 in determining the phenotypic attributes, functional quality, and maintenance of antiviral cd8 t cells following acute infection with the prototypic mouse pathogen lymphocytic choriomeningitis virus. previous reports have documented an obligatory role for il-21 in sustaining cd8 t cell responses during chronic infections. here we show that the r ... | 2010 | 20844201 |
| differential microenvironment localization of effector and memory cd8 t cells. | cd8 t cells are critical for the clearance of intracellular pathogens. upon infection, naive cd8 t cells differentiate into effector cells that target and eliminate infected cells. following clearance of the pathogen, most effector cells die, although a small fraction survives to establish a memory population. subsequent exposure to the same pathogen induces a rapid response of memory t cells and efficient elimination of the pathogen. although much is known about the cd8 t cell response, the pre ... | 2008 | 18097030 |
| card6 is interferon inducible but not involved in nucleotide-binding oligomerization domain protein signaling leading to nf-kappab activation. | we have previously reported the cloning and characterization of card6, a caspase recruitment domain (card)-containing protein that is structurally related to the interferon (ifn)-inducible gtpases. card6 associates with microtubules and with receptor-interacting protein 2 (rip2). rip2 mediates nf-kappab activation induced by the intracellular nucleotide-binding oligomerization domain (nod) receptors that sense bacterial peptidoglycan. here we report that the expression of card6 and rip2 in bone ... | 2008 | 18160713 |
| irak-4 kinase activity is required for irak-4-dependent innate and adaptive immune responses. | interleukin-1 receptor-associated kinase (irak)-4 is a serine-threonine kinase that plays an important role in innate and adaptive immune responses. while the requirement of irak-4 kinase activity has been studied in the context of il-1r signaling, it is not clear whether irak-4 requires its kinase function for all of its roles in the immune system. irak-4 kinase-dead knock-in (irak-4kd/kd) mice were generated to further elucidate whether irak-4 kinase activity is required for irak-4 to induce c ... | 2008 | 18286567 |
| enhancing therapeutic vaccination by blocking pd-1-mediated inhibitory signals during chronic infection. | therapeutic vaccination is a potentially promising strategy to enhance t cell immunity and viral control in chronically infected individuals. however, therapeutic vaccination approaches have fallen short of expectations, and effective boosting of antiviral t cell responses has not always been observed. one of the principal reasons for the limited success of therapeutic vaccination is that virus-specific t cells become functionally exhausted during chronic infections. we now provide a novel strat ... | 2008 | 18332181 |
| formation of il-7ralphahigh and il-7ralphalow cd8 t cells during infection is regulated by the opposing functions of gabpalpha and gfi-1. | il-7 is essential for the survival of naive and memory t cells, and il-7 receptor alpha-chain (il-7ralpha) expression is dynamically regulated in activated cd8 t cells during acute viral and bacterial infections. most virus-specific cd8 t cells become il-7ralpha(low) and are relatively short-lived, but some escape il-7ralpha repression (referred to as il-7ralpha(high) memory precursor effector cells) and preferentially enter the memory cd8 t cell pool. how antiviral effector cd8 t cells regulate ... | 2008 | 18390712 |
| overexpression of lymphotoxin in t cells induces fulminant thymic involution. | activated lymphocytes and lymphoid-tissue inducer cells express lymphotoxins (lts), which are essential for the organogenesis and maintenance of lymphoreticular microenvironments. here we describe that t-cell-restricted overexpression of lt induces fulminant thymic involution. this phenotype was prevented by ablation of the lt receptors tumor necrosis factor receptor (tnfr) 1 or lt beta receptor (ltbetar), representing two non-redundant pathways. multiple lines of transgenic ltalphabeta and ltal ... | 2008 | 18483211 |
| brief report: lymphocytic choriomeningitis virus transmitted through solid organ transplantation--massachusetts, 2008. | lymphocytic choriomeningitis virus (lcmv) is a rodent-borne arenavirus found worldwide. house mice (mus musculus) are the natural reservoir, but lcmv also can infect other wild, pet, and laboratory rodents (e.g., rats, mice, guinea pigs, and hamsters). humans can be infected through exposure to rodent excreta. person-to-person transmission has occurred only through maternal-fetal transmission and solid organ transplantation. lcmv infection in humans can be asymptomatic or cause a spectrum of ill ... | 2008 | 18650788 |
| anti-thymoglobulin (atg) treatment does not reverse type 1 diabetes in the acute virally induced rat insulin promoter-lymphocytic choriomeningitis virus (rip-lcmv) model. | immune modulators such as anti-thymoglobulin (atg) are under clinical evaluation for the treatment of type 1 diabetes (t1d). although such agents have cured t1d in the non-obese diabetic (nod) model, their clinical efficacy has been much lower. in order to improve the odds of successful translation from bench to bedside, we propose to evaluate this agent under more stringent conditions. here, we evaluated the capacity of atg to reverse t1d in the acute rat insulin promoter-lymphocytic choriomeni ... | 2011 | 21235534 |
| killing of targets by cd8 t cells in the mouse spleen follows the law of mass action. | it has been difficult to correlate the quality of cd8 t cell responses with protection against viral infections. to investigate the relationship between efficacy and magnitude of t cell responses, we quantify the rate at which individual cd8 effector and memory t cells kill target cells in the mouse spleen. using mathematical modeling, we analyze recent data on the loss of target cells pulsed with three different peptides from the mouse lymphocytic choriomeningitis virus (lcmv) in mouse spleens ... | 2011 | 21283669 |
| cross-dressed dendritic cells drive memory cd8+ t-cell activation after viral infection. | after an infection, cytotoxic t lymphocyte precursors proliferate and become effector cells by recognizing foreign peptides in the groove of major histocompatibility complex (mhc) class i molecules expressed by antigen-presenting cells (apcs). professional apcs specialized for t-cell activation acquire viral antigen either by becoming infected themselves (direct presentation) or by phagocytosis of infected cells, followed by transfer of antigen to the cytosol, processing and mhc class i loading ... | 2011 | 21455179 |
| immunopathological basis of lymphocytic choriomeningitis virus-induced chorioretinitis and keratitis. | the infection of humans with the rodent-borne lymphocytic choriomeningitis virus (lcmv) can lead to central nervous system disease in adults or severe neurological disease with hydrocephalus and chorioretinitis in children infected congenitally. although lcmv-induced meningitis and encephalitis have been studied extensively, the immunopathological mechanisms underlying lcmv infection-associated ocular disease remain elusive. we report here that the intraocular administration of the neurotropic l ... | 2009 | 18945766 |
| memory cd8 t-cell compartment grows in size with immunological experience. | memory cd8 t cells, generated by natural pathogen exposure or intentional vaccination, protect the host against specific viral infections. it has long been proposed that the number of memory cd8 t cells in the host is inflexible, and that individual cells are constantly competing for limited space. consequently, vaccines that introduce over-abundant quantities of memory cd8 t cells specific for an agent of interest could have catastrophic consequences for the host by displacing memory cd8 t cell ... | 2009 | 19005468 |
| anterograde or retrograde transsynaptic labeling of cns neurons with vesicular stomatitis virus vectors. | to understand how the nervous system processes information, a map of the connections among neurons would be of great benefit. here we describe the use of vesicular stomatitis virus (vsv) for tracing neuronal connections in vivo. we made vsv vectors that used glycoprotein (g) genes from several other viruses. the g protein from lymphocytic choriomeningitis virus endowed vsv with the ability to spread transsynaptically, specifically in an anterograde direction, whereas the rabies virus glycoprotei ... | 2011 | 21825165 |
| evidence of lymphocytic choriomeningitis virus (lcmv) in domestic mice in gabon: risk of emergence of lcmv encephalitis in central africa. | lymphocytic choriomeningitis virus (lcmv) can cause acute fatal disease on all continents but was never detected in africa. we report the first detection of lcmv rna in a common european house mouse (mus musculus domesticus) in africa. phylogenetic analyses show a close relationship with north american strains. these findings suggest that there is a risk of the appearance of lcmv acute encephalitis cases. this is a perfect example of virus dissemination by its natural host that may have dramatic ... | 2015 | 25378495 |
| 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 |
| notes from the field: lymphocytic choriomeningitis virus infections in employees of a rodent breeding facility--indiana, may-june 2012. | in late april 2012, an infectious disease physician contacted cdc regarding a patient with aseptic meningitis who worked at a rodent breeding facility in indiana. lymphocytic choriomeningitis virus (lcmv) infection was suspected, and lcmv-specific antibody was detected in blood and cerebrospinal fluid from the patient, confirming the diagnosis. lcmv is an arenavirus carried by the common house mouse. persons become infected through close contact with infected rodents, through infected organ tran ... | 2012 | 22895387 |
| exposure to lymphocytic choriomeningitis virus, new york, usa. | to the editor: lymphocytic choriomeningitis virus (lcmv) is an arenavirus carried by the house mouse, mus musculus. human infections can range from mild febrile illness to severe encephalitis and disseminated disease (1). infection during pregnancy is associated with teratogenic effects, including congenital hydrocephalus and chorioretinitis (2). | 2011 | 21762607 |