Regulation of CD4 T cell antigen sensitivity by cytokines

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The immune system contains several cell subsets, including T cells, which must be orchestrated properly in order to defend the host against infection. T cells become activated when they encounter a peptide for which they are specific. In order to become fully activated, T cells need to receive at least three different signals. Among these are signals delivered by small proteins generated over the course of an infection, called cytokines. Cytokines are becoming more and more understood to play a critical role in the biology of T cells. We are interested in how these signals are integrated by T cells to regulate their function. In particular, we are interested in how one type of T cells, CD4 T cells, integrate signals from cytokines differently than another related cell type, CD8 T cells. Thus, the main goal of our research program is to understand the impact of cytokine signaling on the biology of CD4 T cells and to elucidate the pathways that are activated downstream of these signals. We will address whether changes in the quality, quantity and timing of signals transmitted by cytokines differentially impact the function of CD4 T cells. In particular, in this research proposal we will concentrate on how signals from cytokines can help CD4 T cells to respond to low concentrations of antigen, a characteristic called antigen sensitivity. Our work will provide novel knowledge that will help us understand how all the signals that T cells receive work together to regulate their function. Understanding the impact of cytokine signaling on CD4 T cells will provide a platform for the development of new biotechnologies to manipulate CD4 T cell function. Thus, this research will yield important intellectual and economic dividends for Canada.