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 of radiation leukemia virus (RadLV)-transformed thymocyte clones induced 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) thymocyte clone. TEC-derived conditioned medium did not mimic the signal induced by TEC in PD1.6 cells. However, the TEC-resistant clone B10 apoptosed in response to TEC, provided that PD1.6 cells were also present in the culture. This effect on bystander cells suggests that a secreted factor was involved. The involvement of glucocorticoid hormones as potential mediators was addressed. PD1.6 cells apoptosed in response to dexamethasone or a cell-permeating analog of cAMP, while BIO cells were relatively resistant to dexamethasone. TcR cross-linking inhibited both TEC- and dexamethasone- but not cAMP-induced apoptosis. Aminoglutethimide and Ru38486 inhibited TEC-induced apoptosis of PD1.6 cells, whereas Ru28318 had a negligible effect. The results suggest that steroid hormones are involved in TcR-independent apoptosis of immature double-positive thymocyte clones induced by TEC.
Zilberman
Y
Y
Department of Pharmacology, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel.
Yefenof
E
E
Oron
E
E
Dorogin
A
A
Guy
R
R
D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002999:Clone Cells; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000502:physiology*; D008223:Lymphoma / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D012995:Solubility; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D011948:Receptors, Antigen, T-Cell; D000616:Aminoglutethimide; D015735:Mifepristone; D003907:Dexamethasone