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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Study Section
Innate Immunity and Inflammation Study Section (III)
Program Officer
Ferguson, Stacy E
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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Hirai-Yuki, Asuka; Hensley, Lucinda; McGivern, David R et al. (2016) MAVS-dependent host species range and pathogenicity of human hepatitis A virus. Science 353:1541-1545
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