INDUCTION OF APOPTOSIS AND P53 EXPRESSION IN IMMATURE THYMOCYTES BY DIRECT INTERACTION WITH THYMIC EPITHELIAL-CELLS

Apoptosis of normal thymocytes was shown to be triggered by several me chanisms (e.g. glucocorticoids, gamma-irradiation). In the present stu dy the authors report on thymocyte apoptosis that is induced by th mie epithelial cells, The thymocytes undergo a massive apoptotic death wi thin 24 h of cocultivation with thymic epithelial cell monolayers deri ved from primary cultures (PTEC) or from a thymic epithelial cell line (TEC). Non-thymic monolayers were inactive, Apoptosis induction in th is experimental model requires direct contact between the thymocytes a nd the thymic epithelial monolayer and tan be blocked by anti-CD2 and anti-LFA-1 antibodies. The immature CD3(-/+dull) CD4(+)CD8(+) thymocyt es were the cells which undergo apoptosis. The fact that the authors a re dealing with a massive apoptotic process of immature cells in the a bsence of exogenous antigen suggests that it involves the nonselected thymocytes. The apoptotic pathway selected by thymocytes following the ir culturing on TEC involves p53 expression. Indeed it was found that TEC-induced apoptosis, led to the accumulation of p53 protein that pre ceded the step of DNA fragmentation in freshly isolated thymocytes as well as in a glucocorticoid resistant thymoma cell line. Since glucoco rticoid-induced thymocyte apoptosis is p53-independent, glucocorticoid s are conceivably not involved in TEC-induced thymocyte death. The in vitro experimental model presented here may reflect the physiological sequence of events leading to thymocyte death in the thymus.