Contextual manipulation of the IL-6 family of cytokines to alter and enhance CD4+ T cell immunity to respiratory viral infections. (360G-Wellcome-101372_Z_13_Z)

By achieving the following research goals I hope to determine the function and protective capacity of the IL-6 family of cytokines during respiratory viral infections: Specific goal #1: To determine the importance of IL-6 and other members of the IL-6 cytokine family in T FH development and humoral immunity. I will use a series of conditional cytokine receptor knockout mice to determine the role of the IL-6 family of cytokines during respiratory viral infection. Specific goal #2: To determ ine the mechanisms behind temporally distinct cytokine responses of CD4+ T cells throughout infection. I have found that IL-6 signaling promotes the differentiation of virus specific CD4 T cells into TFH at late, but not early, stages of infection. I will therefore identify the critical molecular mechanisms that modulate this cytokine signaling at the level of signal transduction and transcription. Specific goal #3: To target CD4+ T cells to enhance humoral immunity toward viral infection du ring infancy. By comparing and contrasting infant and adult RSV infection in mice I will determine the effects of age on promoting TFH. I will then attempt to boost immune responses to infant RSV infection by targeting the IL-6/gp130 pathway.