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细胞应答如何产生和维持的理解存在空白。该提议旨在通过表征促炎细胞因子如何控制感染后的初始病毒特异性淋巴细胞应答和记忆细胞的分化来填补这一空白。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进行测试：1）以确定如何干扰素？信号增加峰值CD4 T细胞应答和记忆，2）表征影响记忆细胞分化的促炎细胞因子的早期T细胞竞争，和3）建立IFN？在慢性病毒感染期间维持CD4 T细胞应答。所提出的实验解决了CD4 T细胞控制和记忆细胞分化的基本方面。从这些研究中收集的信息将进一步研究，旨在了解CD4 T细胞调节CD8 T细胞记忆和B细胞记忆。长期的研究目标是最终确定特定的分子途径，可以靶向增强疫苗诱导的T细胞记忆。 疫苗通过增加病原体特异性白色血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.