Regulation of T cell immunity to viral infection

总结： 幼稚T细胞具有分化为效应细胞的潜力，这些效应细胞具有一系列功能， 病原体以及长寿的记忆细胞，提供保护，防止再次感染。CD4+效应细胞或T辅助细胞 细胞由它们产生的细胞因子定义，细胞因子介导先天性、B细胞和CD8+ T细胞的活性 免疫力大量CD4+辅助性T细胞亚群的存在使确定T细胞亚群的能力变得复杂。 效应和记忆前体群体之间的关系，并确定所需的分子介质 以支持CD4+保护性免疫的形成。由于CD4+ T细胞需要帮助维持CD8+ T细胞 记忆在许多情况下，以支持高亲和力的记忆B细胞反应，并直接活动的先天 细胞，我们将试图定义CD4+记忆T细胞群及其前体， 转录网络驱动免疫记忆的这一重要组成部分的分化和稳态。 此外，我们的研究将探索CD4+记忆T细胞群的不同分化要求， 存在于非淋巴组织和循环记忆群体中。组织驻留记忆细胞是 在疫苗接种的情况下特别感兴趣，因为它们在屏障表面提供基本的哨兵保护， 现在，人们清楚地认识到，在许多感染情况下，他们是“第一反应者”。使用单细胞 蛋白质和基因表达分析，基因组和计算方法，以及体内功能 筛选以及传统的过继转移细胞，所述细胞可以报告表达或突变为 候选监管机构，我们将全面研究CD4+记忆T细胞的形成，以应对病毒 感染这些研究将为开发这种重要记忆T细胞的保护能力提供基础 群体和调节免疫病理学背景下的活性。直接靶向特异性转录 在疫苗接种过程中调节剂作为控制诱导免疫的新策略有希望。 !

SUMMARY: Naive T cells have the potential to differentiate into effector cells with a range of functions that aid in clearing pathogens as well as long-lived memory cells that provide protection from reinfection. CD4+ effector or T helper cells are defined by the cytokines they produce, which mediate the activity of innate, B cell, and CD8+ T cell immunity. The presence of numerous CD4+ T helper subsets has complicated the ability to define the relationship between effector and memory-precursor populations and identify the molecular mediators required to support the formation of CD4+ protective immunity. As CD4+ T cell help is required to sustain CD8+ T cell memory in many contexts, to support high-affinity memory B cell responses, and to direct activity of innate cells, we will seek to define the CD4+ memory T cell population(s) and their precursor(s) as well as the transcriptional networks driving differentiation and homeostasis of this vital component of immune memory. Further, our studies will explore the distinct differentiation requirements for CD4+ memory T cell populations that reside in non-lymphoid tissues and circulating memory populations. Tissue-resident memory cells are of particular interest in the context of vaccination as they provide essential sentinel protection at barrier surfaces, and, are now clearly understood to be among the `first responders' in many infection settings. Using single-cell analyses of protein and gene expression, genomic and computational approaches, and in vivo functional screens as well as traditional adoptive transfers of cells that can report expression of or are mutant for candidate regulators, we will comprehensively study CD4+ memory T cell formation in response to viral infection. These studies will provide the basis to exploit the protective capacity of this vital memory T cell population and modulate activity in the context of immunopathology. Direct targeting of specific transcriptional regulators during vaccination holds promise as a novel strategy in the control of induced immunity. !