ABROGATION OF THE SUPPRESSIVE EFFECTS OF DEXAMETHASONE BY PKC ACTIVATION OR CD28 TRIGGERING

The suppressive effect of the glucocorticoid dexamethasone (DEX) on pu rified CD4(+) T cells was found to depend on the activation pathway. I n contrast to anti-CD3- or PHA-induced T cell proliferation, the alter native pathway of T cell activation, i.e., through anti-CD2 and anti-C D28, appeared largely resistant to DEX. By titrating anti-CD28 or the protein kinase C (PKC) activator PMA in the DEX-sensitive systems, it was demonstrated that inhibition by DEX could be abrogated by enhancin g the CD28 signal or by stimulation of the PKC-dependent pathway. Supr aoptimal concentrations of PMA were inhibitory for proliferation and t his effect was partly prevented by DEX. These data suggest that the ou tcome of the effect of DEX on CD4(+) T cells is dependent on the activ ation pathway, in particular the role and composition of the transcrip tion factor AP-1. (C) 1994 Academic Press, Inc.