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.
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.
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|Cook, Kevin D; Whitmire, Jason K (2016) LAG-3 Confers a Competitive Disadvantage upon Antiviral CD8+ T Cell Responses. J Immunol 197:119-27|
|Cook, Kevin D; Shpargel, Karl B; Starmer, Joshua et al. (2015) T Follicular Helper Cell-Dependent Clearance of a Persistent Virus Infection Requires T Cell Expression of the Histone Demethylase UTX. Immunity 43:703-14|
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|Cook, Kevin D; Kline, Hannah C; Whitmire, Jason K (2015) NK cells inhibit humoral immunity by reducing the abundance of CD4+ T follicular helper cells during a chronic virus infection. J Leukoc Biol 98:153-62|
|Misumi, Ichiro; Whitmire, Jason K (2014) IFN-Î» exerts opposing effects on T cell responses depending on the chronicity of the virus infection. J Immunol 192:3596-606|
|Cook, Kevin D; Waggoner, Stephen N; Whitmire, Jason K (2014) NK cells and their ability to modulate T cells during virus infections. Crit Rev Immunol 34:359-88|
|Misumi, Ichiro; Whitmire, Jason K (2014) B cell depletion curtails CD4+ T cell memory and reduces protection against disseminating virus infection. J Immunol 192:1597-608|
|Cook, Kevin D; Whitmire, Jason K (2013) The depletion of NK cells prevents T cell exhaustion to efficiently control disseminating virus infection. J Immunol 190:641-9|
|Misumi, Ichiro; Alirezaei, Mehrdad; Eam, Boreth et al. (2013) Differential T cell responses to residual viral antigen prolong CD4+ T cell contraction following the resolution of infection. J Immunol 191:5655-68|
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