MHC NONRESTRICTED, CD95-INDEPENDENT APOPTOSIS OF IMMATURE THYMOCYTES INDUCED BY THYMIC EPITHELIAL-CELLS

The interaction of thymocytes with thymic epithelial cells in the abse nce of an exogenous antigen was studied in vitro. Thymic, but not sple nic epithelial cells induced apoptosis of thymocytes, Athymic epitheli al cell line(TEC) induced apoptosis of thymocytes but not of splenic T -cells,The target population for TEC-induced death were immature CD4()8(+) (double positive), but not mature single positive thymocytes. TE C also induced DNA fragmentation in day 18 foetal thymocytes, most of which are CD4(+)8(+) cells. Radiation leukemia virus (RadLV)-transform ed thymic lymphoma clones expressing various phenotypes reflected this sensitivity, in that a CD4(+)8(+)3(+) clone apoptosed by thymic epith elial cells or TEC. Other, single positive or double negative clones w ere resistant. Thymocytes from C3H (H-2(k)), C57BL/6 (H-2(b)) and Balb /C (H-2(d)) mice apoptosed equally in response to either C57BL/6 thymi c epithelial cells or TEC (H-2(b) x H-2(d)). Likewise, thymocytes from MRLlpr((-/-)) and B61pr((-/-)) mice, which do not express CD95 were a lso apoptosed by TEC. The data suggest that thymic epithelial cells in duce MHC non-restricted, Fas-independent apoptosis of immature thymocy tes. This response may reflect a mechanism through which thymocytes ex pressing TcR with no affinity to self MHC/peptide complexes are elimin ated.