Inhibition of interleukin 2-induced proliferation of cloned murine T cells by glucocorticoids. Possible involvement of an inhibitory protein.

Abstract

The ability of glucocorticoids to inhibit interleukin 2 (IL 2)-induced T cell proliferation in two cytotoxic T cell (CTL) clones has been studied. A complete inhibition of DNA synthesis by dexamethasone (Dx) could be observed when IL 2-depleted cultures of CTL were either incubated for 6 h with the hormone prior to the addition of IL 2 or treated simultaneously with Dx and a low concentration of IL 2. No significant reduction in the number and affinity of IL 2 receptors was seen after 6 h incubation with Dx. The order of potency observed with the different steroids indicated that this inhibitory effect was mediated through binding to a specific glucocorticoid receptor. The action of these hormones possibly involves the synthesis of an inhibitory protein(s), since the presence of cycloheximide during the incubation with Dx prevented the inhibition of DNA synthesis. Furthermore, supernatant from Dx-treated CTL contained a nondialyzable factor which inhibited DNA synthesis and cell growth of CTL clones induced by IL 2. Blocking of IL 2 synthesis and IL 2 receptor formation have been proposed as one of the major mechanisms of glucocorticoid-induced immunosuppression. Our results indicate that these hormones may also affect T cell proliferation by inhibiting IL 2 activity.