Differential inhibition of the T cell activation pathway by dexamethasone and cyclosporine.
We examined the inhibitory capacity of dexamethasone (DEX) and cyclosporine (CsA) on T cell activation using various accessory cell (AC)-dependent and AC-independent stimuli. We found that CsA strongly inhibited T cell activation in each of the assays used: allogeneic T cell stimulation, phorbol myristate acetate plus concanavalin A, PMA plus anti-CD3 monoclonal antibody (2C11), or PMA plus ionomycin (IONO) T cell activation. DEX was a potent inhibitor of allogeneic stimulation and of the PMA+Con A- or PMA + 2C11-induced T cell stimulation. PMA + IONO stimulation, however, was not affected by DEX. When inhibition occurred, both drugs suppressed [3H]TdR incorporation, IL-2 production, and IL-2 mRNA accumulation, indicating that the sites of interference of these drugs in the T cell activation pathway are located proximal to IL-2 mRNA accumulation. However, the difference in the effects of DEX and CsA in PMA + IONO stimulation suggests that DEX and CsA differentially affect T cell activation.
Furue
M
M
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Kawakami
Y
Y
Kawakami
T
T
Katz
S I
SI
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D003524:Cyclosporins / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003524:Cyclosporins; D007376:Interleukin-2; D012333:RNA, Messenger; D007975:Leukotriene B4; D015759:Ionomycin; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate