Regulation of T lymphocyte apoptosis. Signals for the antagonism between activation- and glucocorticoid-induced death.
Apoptotic death can be induced in T cell hybridomas by glucocorticoids or the stimulation via the TCR/CD3 complex. The two apoptotic processes are mutually antagonistic. We have previously proposed that positive selection of thymocytes for the formation of the T cell repertoire might be based on a similar mechanism. We analyzed the TCR/CD3-mediated signals essential for the regulation of apoptosis in T cell hybridomas. We suggest that both an increase in the intracellular Ca2+ level and an activation of protein kinase C are essential for the TCR/CD3-mediated apoptosis, because we obtained the following results: 1) either reduction of extracellular Ca2+ concentration or addition of a protein kinase inhibitor, 1-(5-isoquinolkinelsulfonyl)-2-methylpiperazine or N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide, inhibited anti-CD3-induced but not dexamethasone-induced DNA fragmentation. 2) The combination of ionomycin and PMA, but neither one alone nor the combination of ionomycin and cyclic nucleotide analogs, induced DNA fragmentation. On the contrary, we suggest that only an increase in the intracellular Ca2+ level is essential for the inhibition of glucocorticoid-induced apoptosis, because ionomycin alone as well as the combination of ionomycin and PMA inhibited dexamethasone- but not anti-CD3-induced DNA fragmentation.
Iseki
R
R
Laboratory of Cellular Immunology, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Mukai
M
M
Iwata
M
M
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002118:Calcium / Q000502:physiology*; D016923:Cell Death; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation; D006825:Hybridomas / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D015759:Ionomycin; D003907:Dexamethasone; D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium