ABSTRACT Previous studies have shown that some respiratory virus infections leave local populations of tissue TRM cells in the lungs which disappear as heterosubtypic immunity declines. The location these and their contribution to protective CTL response not been clearly defined. Here, fluorescence microscopy is used show CD103+ remain embedded walls large airways long after pulmonary immunization but are absent from systemically primed mice. Viral clearance locally immunized mice precedes...

Abstract Lymphocyte activation gene-3 (LAG-3) is a CD4-related, activation-induced cell surface molecule that binds to MHC class II with high affinity. In this study, we used four experimental systems reevaluate previous suggestions LAG-3−/− mice had no T defect. First, cells exhibited delay in cycle arrest following vivo stimulation the superantigen staphylococcal enterotoxin B resulting increased expansion and splenomegaly. Second, was also observed adoptive recipients of OT-II TCR...

Abstract Following activation within secondary lymphoid tissue, CD8 T cells must migrate to targets, such as infected self allografts, and tumors, mediate contact-dependent effector functions. To test whether the pattern of migration activated was dependent on site Ag encounter, we examined distribution mouse Ag-specific following local challenges. Our findings indicated that migrated pervasively all nonlymphoid organs irrespective initial engagement. Using an adoptive transfer system,...

Viral infections often gain access to the body of their host by exploiting areas natural vulnerability, such as semipermeable surfaces mucosal tissues which are adapted for adsorption nutrients and other diffusible molecules. Once microbes have crossed epithelial barrier, they can disperse where eradication may not be possible. The best opportunity successful immune intervention is immediately after infection while pathogen confined a localized area body. Cytotoxic T lymphocytes (CTL) reside...

CD8+ tissue-resident memory T cells (TRM cells) are poised at the portals of infection and provide long-term protective immunity. Despite their critical roles, precise mechanics governing TRM cell reactivation in situ unknown. Using a TCR-transgenic Nur77-GFP reporter to distinguish "antigen-specific" from "bystander" reactivation, we demonstrate that lung reactivated more quickly, yet less efficiently, than counterparts draining LNs (TLN cells). Global profiling revealed tissue-defined...

Abstract Previous studies have shown that heterologous viral infections a significant impact on pre-existing memory T cell populations in secondary lymphoid organs through combination of cross-reactive and bystander effects. However, the effector/memory cells peripheral sites is not well understood. In this study, we analyzed influenza virus infection Sendai virus-specific CD8+ present lung airways. The data show transient increase numbers nucleoprotein 324–332/Kb-specific airways...

The initial engagement of the TCR through interaction with cognate peptide-MHC is a requisite for T cell activation and confers Ag specificity. Although this key event in activation, duration these interactions may affect proliferative capacity differentiation activated cells. In study, we developed system to evaluate temporal requirements antigenic stimulation during an immune response vivo. Using Abs that target specific Ags context MHC, were able manipulate availability both CD4 CD8 cells...

Abstract Recent studies have shown that virus-specific effector memory T cells can be recovered from the lung airways long after clearance of a respiratory virus infection. These are thought to play an important role in recall response secondary viral It is currently unclear whether these actually persist at this site or maintained by continual proliferation and recruitment. In study, we analyzed mechanisms underlying persistence CD8+ airway lumina following recovery The data identify two...

ABSTRACT Long-term antigen expression is believed to play an important role in modulation of T-cell responses chronic virus infections. However, recent studies suggest that immune may occur late after apparently acute We have now analyzed the CD8 response vesicular stomatitis (VSV), which thought cause infection characterized by rapid clearance innate and adaptive system components. Unexpectedly, virus-encoded was detectable more than 6 weeks intranasal VSV both draining nondraining lymph...

Tissue-resident memory CD8 T cells are a unique subset of virus-specific CTLs that bolster local immune responses after becoming lodged in previously infected tissues. These provide enhanced protection by intercepting returning pathogens before new infection gets established. In contrast, central circulate the bloodstream and proliferate secondary lymphoid organs replenishing effector cell populations remote parts body. Both participate immunity to influenza virus infection; however,...

Abstract We have previously shown that systemic staphylococcal enterotoxin A (SEA) injections cause CD4 T cells in TCR-transgenic mice to become tolerant subsequent ex vivo restimulation. An active IFN-γ-dependent mechanism of suppression was responsible for the apparent unresponsiveness cells. In this study, we analyze response isolated throughout first 10 days injected SEA. show at peak undergo very little activation-induced cell death after sterile FACS sorting or restimulation presence...

Abstract Recent studies have shown that CD4+ memory T cells persist in nonlymphoid organs following infections. However, the development and phenotype of these peripheral are poorly defined. In this study, multimerized MHC-Ig fusion proteins, with a covalently attached peptide sequence from Sendai virus hemagglutinin/neuraminidase gene, been used to identify virus-specific during infection establishment populations lungs. We show declining frequencies lungs over course ∼3 mo after infection....

Abstract CD134- and CD137-primed CD8 T cells mount powerful effector responses upon recall, but even without recall these dual-costimulated respond to signal 3 cytokines such as IL-12. We searched for alternative receptor pathways found the IL-1 family member IL-36R. Although IL-36 alone did not stimulate cells, in combination with IL-12, or more surprisingly IL-2, it induced striking rapid TCR-independent IFN-γ synthesis. To understand how functioned we showed that IL-2 IL-36R gene...

Influenza virus is a significant cause of mortality and morbidity in children; however, little known about the T cell response infant lungs. Neonatal mice are highly vulnerable to influenza only control very low doses virus. We compared infection between infected as adults or at 2 d old observed defective migration into lungs neonatal mice. In adult mice, numbers cells lung interstitia peaked 10 postinfection, whereas infiltration, activation, expression TNF-alpha was delayed until wk...

Bacterial superantigens induce peripheral unresponsiveness in CD4+ T cell populations that express appropriate Vbeta chains. We have used Vbeta3/Valpha11 receptor transgenic (Tg) mice and the Vbeta3-specific superantigen staphylococcal enterotoxin A (SEA) to further investigate mechanisms contribute such unresponsiveness. As other models, vivo exposure SEA rendered Tg cells unresponsive subsequent restimulation vitro with antigen or mitogens. However, when SEA-treated were completely...

Pulmonary influenza infection causes prolonged lymph node hypertrophy while processed viral antigens continue to be presented virus-specific CD8 T cells. We show that naïve, but not central/memory, nucleoprotein (NP)-specific cells recognized antigen-bearing CD11b(+) DC in the draining nodes more than 30 days after infection. After these late transfers, naïve underwent an abortive proliferative response mediastinal (MLN), where large clusters of partially activated remained paracortex until...

Cross-protection between serologically distinct strains of influenza A virus (IAV) is mediated by memory CD8 T cells that recognize epitopes from conserved viral proteins. Early control begins with activation tissue-resident (TRM) at the site replication. These do not act in isolation, as protection against disseminated infection reinforced multiple waves effector (TEFF) enter lungs different kinetics. To define how a protective CTL response evolves, we compared functional properties...

Cytotoxic T lymphocytes (CTLs) are important targets for vaccines against a wide variety of infections that enter the body via mucosal tissues. To induce effective immunity these must include most protective epitopes and elicit rapid recall responses at site infection. Although live attenuated viruses sometimes used to cellular recurrent influenza infections, mechanisms determine magnitude response individual viral components very poorly defined. Heterosubtypic in C57BL/6 mice illustrate an...