T-CELL RECEPTOR-INDEPENDENT APOPTOSIS OF THYMOCYTE CLONES INDUCED BY A THYMIC EPITHELIAL-CELL LINE IS MEDIATED BY STEROIDS

We have studied the mechanisms involved in TcR-independent apoptosis o f radiation leukemia virus (RadLV)-transformed thymocyte clones induce d by a thymic epithelial cell line (TEC). TEC induced apoptosis of an immature CD4(+)8(+)3(+) (PD1.6) but not of a CD4(-)8(-)3(-) (B10) thym ocyte clone. TEC-derived conditioned medium did not mimic the signal i nduced by TEC in PD1.6 cells. However, the TEC-resistant clone B10 apo ptosed in response to TEC, provided that PD1.6 cells were also present in the culture. This effect on bystander cells suggests that a secret ed factor was involved. The involvement of glucocorticoid hormones as potential mediators was addressed. PD1.6 cells apoptosed in response t o dexamethasone or a cell-permeating analog of cAMP, while B10 cells w ere relatively resistant to dexamethasone. TcR cross-linking inhibited both TEC- and dexamethasone- but not cAMP-induced apoptosis. Aminoglu tethimide and Ru38486 inhibited TEC-induced apoptosis of PD1.6 cells, whereas Ru28318 had a negligible effect, The results suggest that ster oid hormones are involved in TcR-independent apoptosis of immature dou ble-positive thymocyte clones induced by TEC. (C) 1996 Academic Press, Inc.