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

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Abstract
The ability of glucocorticoids to inhibit interleukin 2 (IL2)-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 IL2-depleted cultures of CTL were either incubated for 6 h with the hormone prior to the addition of IL2 or treated simultaneously with Dx and a low concentration of IL2. No significant reduction in the number and affinity of IL2 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 IL2. Blocking of IL2 synthesis and IL2 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 IL2 activity.