Loss of lymphocytes, particularly T cell apoptosis, is a central pathological event after severe tissue injury which is associated with increased susceptibility for life-threatening infections. The precise immunological mechanisms leading to T cell death after acute injury are largely unknown. Here, we identified a monocyte-T cell interaction driving bystander cell death of T cells in ischemic stroke and burn injury. Specifically, we found that stroke induced a FasL-expressing monocyte population, which led to extrinsic T cell apoptosis. This phenomenon was driven by the AIM2 inflammasome-dependent interleukin-1 (IL-1 ) secretion after sensing cell-free DNA. Pharmacological inhibition of this pathway improved T cell survival and reduced post-stroke bacterial infections. As such, this study describes inflammasome-dependent monocyte activation as a previously unstudied cause of T cell death after injury, and challenges the current paradigms of post-injury lymphopenia.

This study compares first-generation and continuing-generation female college students in terms of: (a) level of parents' emotional and informational support; (b) level of students' stress; and (c) the relationship between both types of parent support and students' stress during the transition to college. We collected survey data from an ethnically diverse sample of 339 young women about to enter college. Results indicate first-generation students perceive less emotional and informational parent support than do continuinggeneration students. First-generation students who perceive higher levels of parent emotional support have less stress than those who do not. However, neither type of parent support significantly predicted stress levels for continuing-generation students.

20Cytomegalovirus (CMV) is a ubiquitous β-herpesvirus that establishes life-long latent infection 21 in a high percentage of the population worldwide. CMV induces the strongest and most durable 22 CD8 + T cell response known in human clinical medicine. Due to its unique properties, the virus 23 represents a promising candidate vaccine vector for the induction of persistent cellular 24 immunity. To take advantage of this, we constructed a recombinant murine CMV (MCMV) 48 but only if we administered it through the nose, to activate killer T cells that will persist in the 49 lungs close to the airways. Therefore, our data show that the subset of lung-resident killer T 50 cells is sufficient to protect against influenza. 3 51 Introduction 52 Respiratory infections caused by influenza viruses usually are associated with mild-to-53 moderate disease symptoms but are linked with high morbidity and mortality in susceptible 54 populations like the elderly, young children, patients with co-morbidities and 55 immunocompromised patients. Influenza virus causes seasonal epidemics, with typically 3 to 56 5 million cases of severe illness worldwide, according to WHO reports [1], and influenza type 57 A viruses (IAV) cause the more severe disease form. Vaccines against influenza are based on 58 the induction of adaptive immunity that targets the projected yearly epidemics. While most 59 vaccines are based on inactivated IAV formulations inducing anti-IAV IgG responses, live 60 attenuated influenza vaccines (LAIV) are also used as formulations for i.n. administration. This 61 is based on the assumption that the induction of local immunity may provide superior immune 62 protection [2, 3]. However, it remains unclear whether this protection depends on local IgA 63 responses, on cytotoxic T cell responses, or on their combined antiviral activity. Of note, 64 functional T cell responses were shown to substantially contribute to antiviral IAV immunity [4-65 6]. In particular, cytotoxic influenza-specific CD8 + T lymphocytes (CTLs) promote viral 66 clearance indirectly by secretion of pro-inflammatory cytokines such as IFNγ [7] and directly 67 by perforin/Fas-mediated killing of infected epithelial cells in the bronchoalveolar space [8]. 68 However, it remained unclear if T cell responses alone may control IAV, or if Ig responses were 69 the crucial contributor to LAIV-mediated immune protection. We considered that this question 70 could be addressed by developing a vaccine formulation that optimizes T cell responses 71 against IAV, while excluding the humoral ones. 72 CMV infection induces sustained functional T cell responses that are stronger in the long-term 73 than the immune response to any other infectious pathogen [9]. Experiments in the mouse 74 model have shown that defined CMV epitope-specific CD8 + T cells accumulate in tissues and 75 blood and are maintained at stable high levels during mouse CMV (MCMV) latency [10]. This 76 phenomenon was termed ''Memory Inflation'' [11]. While some MCMV derived peptides, as the 77 ones de...

The innate immune system senses influenza A virus (IAV) through different pathogen-recognition receptors including Toll-like receptor 7 (TLR7). Downstream of viral recognition natural killer (NK) cells are activated as part of the anti-IAV immune response. Despite the known decisive role of TLR7 for NK cell activation by therapeutic immunostimulatory RNAs, the contribution of TLR7 to the NK cell response following IAV infection has not been addressed. We have analyzed lung cytokine responses as well as the activation, interferon (IFN)-γ production, and cytotoxicity of lung and splenic NK cells following sublethal respiratory IAV infection in wild-type and TLR7ko mice. Early airway IFN-γ levels as well as the induction of lung NK cell CD69 expression and IFN-γ production in response to IAV infection were significantly attenuated in TLR7-deficient hosts. Strikingly, respiratory IAV infection also primed splenic NK cells for IFN-γ production, degranulation, and target cell lysis, all of which were fully dependent on TLR7. At the same time, lung type I IFN levels were significantly reduced in TLR7ko mice early following IAV infection, displaying a potential upstream mechanism of the attenuated NK cell activation observed. Taken together, our data clearly demonstrate a specific role for TLR7 signaling in local and systemic NK cell activation following respiratory IAV infection despite the presence of redundant innate IAV-recognition pathways.