INTRACELLULAR SIGNALS THAT MEDIATE THYMIC NEGATIVE SELECTION

Antigenic stimulation of CD4/CD8 double positive (DP) thymocytes results in programmed cell death, while the identical stimulation of mature T cells results in proliferation and lymphokine secretion. Using thymocytes from transgenic mice expressing pigeon cytochrome c-specific T cell receptors, we previously demonstrated that major histocompatibility complex class Il-transfected L cells were capable of presenting peptide antigen and inducing programmed cell death in DP thymocytes, as well as proliferation and lymphokine secretion in mature CD4 single positive (SP)T cells. We therefore were interested in utilizing this system to compare antigen-induced signal transduction events in DP thymocytes and mature SP T cells. In this report, we demonstrate that significant distinctions between thymocytes and mature T cells are seen upon examination of antigen sensitivity and the phosphatidylinositol signaling cascade.