T Cell Receptor-Dependent Regulation of Lipid Rafts Controls Naive CD8+ T Cell Homeostasis

SummaryT cell receptor (TCR) contact with self ligands keeps T cells alive and is shown here to cause naive CD8+, but not CD4+, T cells to be hypersensitive to certain γc cytokines, notably interleukin (IL)-2, IL-15, and IL-7. Hypersensitivity of CD8+ T cells to IL-2 was dependent on a low-level TCR signal, associated with high expression of CD5 and GM1, a marker for lipid rafts, and was abolished by disruption of lipid rafts. By contrast, CD4+ T cells expressed low amounts of GM1 and were unresponsive to IL-2. Physiologically, sensitivity to IL-7 and IL-15 maintains survival of resting CD8+ T cells, whereas sensitivity to IL-2 may be irrelevant for normal homeostasis but crucial for the immune response. Thus, TCR contact with antigen upregulates GM1 and amplifies responsiveness of naive CD8+ T cells to IL-2, thereby making the cells highly sensitive to exogenous IL-2 from CD4+ T helper cells