Interferon-gamma increases CD4+ T cell survival and proliferation

Recent investigations have revealed that cooperation between innate and adaptive immunity is important in initiating and sustaining an effective immune response against a pathogen. However, the role of the proinflammatory cytokine Interferon-gamma (IFN-gamma) in bridging the innate and adaptive immune response is not fully understood. IFN-gamma is secreted in large quantities by natural killer cells during the innate immune response and by activated cluster differentiation four positive T cells (CD4+ T cells) during the adaptive immune response. The major IFN-gamma cell signaling pathway involves signal transducer and activator of transcription 1 (STAT1) and controls the expression of a large number of genes in innate and adaptive immunity. Here, I demonstrate that IFN-gamma aids in initiating an effective adaptive immune response by leading to higher levels of CD4+ T cell proliferation in response to antigenic stimulation. This increase in proliferation occurs through a STAT1-independent signaling pathway and does not correlate to increased signaling through the T cell receptor in response to antigenic stimulation. In contrast, I have shown that IFN-gamma increases CD4+ T cell survival independent of antigenic stimulation. My findings suggest that IFN-gamma may enhance the advent of adaptive immunity by ensuring the survival of CD4+ T cells. (Abstract shortened by UMI.)...