Immature CD4(+)CD8(+) thymocytes do not polarize lipid rafts in response to TCR-mediated signals

TCR-mediated stimulation induces activation and proliferation of mature T c ells. When accompanied by signals through the costimulatory receptor CD28, TCR signals also result in the recruitment of cholesterol- and glycosphingo lipid-rich membrane microdomains (lipid rafts), which are known to contain several molecules important for T cell signaling. Interestingly, immature C D4(+)CD8(+) thymocytes respond to TCR/CD28 costimulation not by proliferati ng, but by dying. In this study, we report that, although CD4(+)CD8(+) thym ocytes polarize their actin cytoskeleton, they fail to recruit lipid rafts to the site of TCR/CD28 costimulation. We show that coupling of lipid raft mobilization to cytoskeletal reorganization can be mediated by phosphoinosi tide 3-kinase, and discuss the relevance of these findings to the interpret ation of TCR signals by immature vs mature T cells.