Interleukin 2 (IL2) is a glycoprotein hormone that is synthesized and secreted by antigen.activated T lymphocytes. Activation of T cells also results in the expression of high affinity IL2 receptors on the cell surface. Subsequent binding of IL2 drives the unrestricted progression of activated (G1 phase) T cells through the replicative phases of the cell cycle (S, G2, and M). The molecular mechanism(s) by which IL2 regulates T cell cycle progression is largely undefined. The overall objective of this research is to compare IL2 dependent signal transduction in two homogeneous subpopulations of murine T cells, L3T4 positive, and Lyt2 positive T cells. This comparison will permit a distinction to be drawn between the molecular events involved in the common mitogenic pathway and events that may reflect subset.specific pleiotropic actions of IL2. The immediate goals of this research are, (1) to examine the effect of IL2 on phosphoinositide turnover, calcium mobilization, and protein kinase C activation in activated L3T4 positive and Lyt2 positive T cells, (2) to characterize the early effects of IL2 on second messenger activated protein kinases and, (3) to determine whether IL2 stimulation specifically and differentially increases the expression of specific genes in G1.phase L3T4 positive and Lyt2 positive T cells. These studies will define the early molecular events involved in the transmission of the IL2 mitogenic signal in two well defined T cell subsets. The results will help to clarify the roles of these signal transmission pathways in the coupling between membrane IL2 receptors and the responses in the cell nuclei that culminate in T cell proliferation.
