Glucocorticoids activate a suicide program in mature T lymphocytes: protective action of interleukin-2.
Viability of T cell blasts obtained by concanavalin A stimulation of mouse spleen cells markedly decreases when these cells are exposed to glucocorticoid hormones in the absence of interleukin-2. The mechanism underlying the lysis of the mature lymphocytes seems to correspond to the apoptotic type of cell death inasmuch as an early degradation of DNA into oligonucleosome-length fragments is observed. Moreover, glucocorticoid-induced DNA fragmentation is delayed in the presence of an inhibitor of protein synthesis. Induction of the cell death program by glucocorticoids is most likely mediated through the interaction with a specific glucocorticoid receptor as suggested by the structure-activity relationship of the various steroids tested. Interestingly, the presence of a saturating dose of IL-2 during the treatment of concanavalin A blasts with glucocorticoids totally abolished DNA fragmentation and cell lysis.
Nieto
M A
MA
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
López-Rivas
A
A
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage; D005938:Glucocorticoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects*
D005938:Glucocorticoids; D007376:Interleukin-2