Resistance of Staphylococcal enterotoxin B- induced proliferation and apoptosis to the effects of dexamethasone in mouse lymphocyte cultures.
Staphylococcal enterotoxin B (SEB) is a superantigen causing lymphocyte proliferation and apoptosis. Glucocorticoids are immunosuppressants and are released immediately following SEB intoxication in mice. Whether glucocorticoids affect lymphocyte proliferation and apoptosis in SEB-intoxicated mice is still unknown. To study this question, we examined the effects of dexamethasone (DEX), a synthetic glucocorticoid, on SEB-stimulated lymphocyte cultures from mouse thymus and peripheral lymphoid tissues (PLT). SEB, as well as concanavalin A (Con A), induced lymphocyte proliferation which peaked on day 4 and declined significantly on day 7. As expected, in Con A-stimulated cultures, DEX completely suppressed the proliferation of lymphocytes from both the thymus and PLT. However, in SEB-stimulated cultures, while DEX completely suppressed thymocyte proliferation, it did not suppress PLT cell proliferation even at a high concentration of 10(-7) M. The proliferating cells were Vbeta8(+) T cells of both the CD4(+) and CD8(+) subsets. DEX caused apoptosis. SEB also caused apoptosis, which was manifested by a maximal DNA subdiploidy on day 4 and by a maximal DNA fragmentation on day 7. Both events appeared not to be affected by DEX. The failure of DEX to affect the proliferation and apoptosis was consistent with high levels of cytokines (IL-1alpha, IL-2, IL-4, IL-6 and IFN-gamma) produced in the SEB-stimulated cultures, suggesting that the cytokines act in concert to circumvent the effects of DEX.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000494:pharmacology*; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018089:Superantigens / Q000494:pharmacology*