Critical function of T cell death-associated gene 8 in glucocorticoid-induced thymocyte apoptosis

Abstract

Transcriptional expression of a gene or genes is absolutely required for induction of glucocorticoid‐induced thymocyte apoptosis. We have previously shown that expression of T cell death‐associated gene 8 (TDAG8) is quickly induced exclusively in the thymus after dexamethasone (DEX) treatment. Here, we present data that TDAG8 expression is induced prior to induction of DEX‐mediated apoptosis. In contrast, TDAG8 expression in thymocytes was not induced in the process of γ‐irradiation‐mediated apoptosis. TDAG8 expression accelerated only DEX‐induced, but not TCR‐mediated or γ‐irradiation‐induced, thymocyte apoptosis in transgenic mice overexpressing TDAG8. Interestingly, these effects were specifically detected in CD4⁺CD8⁺ double‐positive thymocytes. Moreover, activation of caspase‐3, ‐8 and ‐9 was enhanced in thymocytes of TDAG8 transgenic mice after DEX stimulation. In conclusion, TDAG8 expression is involved in glucocorticoid‐induced signals to activate caspase‐9, ‐8 and ‐3 for subsequent apoptosis induction in CD4⁺CD8⁺ double‐positive thymocytes.