Analyses of the effects of pro-inflammatory cytokines on CD4+ T cell responses

描述（由申请人提供）：我们对CD4 T细胞反应如何产生和维持的理解是空白的。这一建议旨在填补这一空白，通过表征促炎细胞因子如何控制感染后初始病毒特异性淋巴细胞反应和记忆细胞的分化。这项研究的基本假设是炎症信号增强了原发性和记忆性T细胞的发育。这将通过追求三个具体目标来检验：1)确定IFN如何？信号增加峰值CD4 T细胞反应和记忆，2)表征早期T细胞对影响记忆细胞分化的促炎细胞因子的竞争，3)建立IFN？在慢性病毒感染期间维持CD4 T细胞反应。提出的实验解决CD4 T细胞控制和记忆细胞分化的基本方面。从这些研究中收集到的信息将进一步研究CD4 T细胞对CD8 T细胞记忆和B细胞记忆的调节。长期研究的目标是最终确定特定的分子途径，这些途径可以通过药理学靶向来增强疫苗诱导的T细胞记忆。

DESCRIPTION (provided by applicant): There is a void in our understanding of how CD4 T cell responses are generated and maintained. This proposal is aimed at filling this void, by characterizing how pro- inflammatory cytokines govern the initial virus-specific lymphocyte response after infection and the differentiation of memory cells. The underlying hypothesis of this grant is that inflammatory signals enhance primary and memory T cell development. This will be tested by pursuing three specific aims: 1) to determine how IFN? signals increase the peak CD4 T cell response and memory, 2) to characterize early T cell competition for pro-inflammatory cytokines that affect memory cell differentiation, and 3) to establish the mechanism(s) by which IFN? sustains CD4 T cell responses during chronic virus infection. The proposed experiments address fundamental aspects of CD4 T cell control and memory cell differentiation. Information gleaned from these studies will further investigations directed at understanding CD4 T cell regulation of CD8 T cell memory and B cell memory. The long-range research goals are to eventually identify specific molecular pathways that can be pharmacologically targeted to enhance vaccine-induced T cell memory. PUBLIC HEALTH RELEVANCE Vaccines protect against infection by increasing the number of pathogen-specific white blood cells. These studies investigate how interferons increase the number of these cells. These experiments will hopefully identify new ways to improve vaccines.