INTRATHYMIC SIGNALS IN THYMOCYTES ARE MEDIATED BY P38 MITOGEN-ACTIVATED PROTEIN-KINASE

Thymocytes develop into mature functional T cells in the inductive env ironment of the thymus where thymocyte-stromal cell interactions and c ytokines provide survival and differentiation signals as cues for thym ocyte maturation. Disruption of the thymic microenvironment results in attenuation of T cell maturation, suggesting that intrathymic signals are essential for differentiation and repertoire selection. We have p reviously shown that several inducible nuclear factors such as AP-1, N F-AT, and NF-kappa B are activated in response to intrathymic signals. Here we demonstrate that in thymocytes p38 mitogen-activated protein (MAP) kinase, a member of the MAP kinase family of proteins that inclu de the extracellular-signal regulated kinases and Jun aminoterminal ki nases, is highly activated in response to intrathymic signals in vivo. These studies suggest a role for p38 MAP kinase in T cell survival an d differentiation.