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. © 1990 by Williams & Wilkins.