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.
|Misumi, Ichiro; Whitmire, Jason K (2014) IFN-? 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|
|Whitmire, Jason K (2011) Induction and function of virus-specific CD4+ T cell responses. Virology 411:216-28|
|Botten, Jason; Whitton, J Lindsay; Barrowman, Polly et al. (2010) A multivalent vaccination strategy for the prevention of Old World arenavirus infection in humans. J Virol 84:9947-56|
|Whitmire, Jason K; Eam, Boreth; Whitton, J Lindsay (2009) Mice deficient in stem cell antigen-1 (Sca1, Ly-6A/E) develop normal primary and memory CD4+ and CD8+ T-cell responses to virus infection. Eur J Immunol 39:1494-504|
|Kemball, Christopher C; Harkins, Stephanie; Whitmire, Jason K et al. (2009) Coxsackievirus B3 inhibits antigen presentation in vivo, exerting a profound and selective effect on the MHC class I pathway. PLoS Pathog 5:e1000618|
|Whitmire, Jason K; Asano, Mary S; Kaech, Susan M et al. (2009) Requirement of B cells for generating CD4+ T cell memory. J Immunol 182:1868-76|