Glucocorticoids regulate TCR-induced elevation of CD4: Functional implications

CD4 serves as a coreceptor during Ag recognition by the TCR, This interacti on results in a marked increase in the sensitivity of a T cell to Ag presen ted by MHC class II molecules, Here we report that activation of T cells ei ther by plate-bound mAb (anti-TCR, anti-CD3) or soluble activators (staphyl ococcal enterotoxin A, Con A) is associated with an (up to 3-fold) increase in CD4 cell surface expression on CD25(+) cells, which was maximal after 7 2-96 h, Incubation with the glucocorticoid hormone corticosterone (CORT) sh ifted the enhancement of CD4 expression to a point about 24 h earlier than that observed in control cultures, In parallel, the proliferative response of these CORT-treated cells was profoundly enhanced. An involvement of incr eased CD4 expression in this enhanced proliferative response was evidenced by the observation that T cell proliferation in CORT-treated cultures was m uch less sensitive to inhibition by an inhibitory, nondepleting anti-CD4 mA b than that in control cultures, TCR down-regulation was, however, not affe cted by CORT, Thus, based on this study and previous reports we propose tha t both TCR-mediated signals and glucocorticoids are important physiological regulators of CD4 expression. In addition, these findings may be of signif icance for the sensitivity of CD4(+) cells to HIV infection upon T cell act ivation, as the efficacy of primary patient HIV entry depends on the level of surface CD4.