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

描述(由申请人提供)：我们对CD4T细胞反应是如何产生和维持的理解是空白的。这项建议旨在通过表征致炎细胞因子如何控制感染后最初的病毒特异性淋巴细胞反应和记忆细胞的分化来填补这一空白。这项拨款的基本假设是，炎症信号促进了初级和记忆性T细胞的发育。这将通过追求三个具体目标来测试：1)确定干扰素是如何？信号增强CD4T细胞反应和记忆的峰值，2)表征早期T细胞竞争影响记忆细胞分化的促炎细胞因子，3)建立机制(S)，通过干扰素？在慢性病毒感染期间维持CD4T细胞反应。建议的实验涉及CD4T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CD8T细胞对CD8T细胞记忆和B细胞记忆的调控。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物靶向来增强疫苗诱导的T细胞记忆。 与公共健康相关的疫苗通过增加病原体特异性白细胞的数量来预防感染。这些研究调查了干扰素如何增加这些细胞的数量。这些实验有望找到改进疫苗的新方法。

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.