To elucidate the mechanisms involved in mouse thymocyte apoptosis induced by thymic epithelial cell-derived soluble factors (TESFs), thymocytes were treated with TESFs or TESFs plus inhibitors of RNA or protein. TESFs were examined for the
selective
elimination of thymocyte subpopulation. The results showed that incubation of thymocytes in TESFs induced DNA fragmentation of CD4+ CD8+ cells in suspension culture for 24hrs, whereas DNA fragmentation was not induced in CD4+ CD8- or CD-4CD8+
cels.
TESFs also suppressed thymocyte responses to mutogen at high concentration. Therefore, TESFs-induced DNA fragmentation is thought to be mediated by prostaglandin E2-like factor secreted from thymic epitherial cells. TESFs-induced DNA
fragmentation
was
inhibited by inhibitors of RNA or protein synthesis, or endonuclease, but was not blocked by PKC inhibitor. In addition, TESFs-induced DNA fragmentaiton was prdevented by splenic mucrophage supernatants, and this inhibition was thought to be
mediated by
interaction (crosstalk) between PKA and PKC. The above results revealed that the more immature thymocytes are, the more susceptible they are to these stinrulators, and suggested that endogenous factors may functlon as a regulator for negative or
positive selection via thymocyte apoptosis.
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