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

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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.