Glucocorticoid-induced inhibition of T cell growth factor production. I. the effect on mitogen-induced lymphocyte proliferation

Gillis, S.; Crabtree, G.R.; Smith, K.A.

Journal of Immunology 123(4): 1624-1631


ISSN/ISBN: 0022-1767
PMID: 314468
Accession: 068526090

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Glucocorticoids inhibit mitogen- or antigen-induced lymphocyte proliferation. The mechanism underlying this effect remains ill-defined. T harvested from TCGF-dependent long-term culture were only mildly sensitive to inhibitory effects (25-30% inhibition) or glucocorticoids as measured by decreased cellular proliferation and the incorporation of 3H thymidine. The degree of inhibition observed was most probably mediated through glucocorticoid receptors in that the half-maximal inhibitory glucocorticoid concentration correlated with half-maximal glucocorticoid receptor saturation. Mitogen-induced TCGF production and T cell proliferation were completely inhibited by pharmacologic concentrations of dexamethasone (10-6 M). The TCGF supplementation of mitogen-stimulated cultures treated with maximal inhibitory concentrations of dexamethasone resulted in complete amelioration of glucocorticoid suppression. A major mechanism of glucocorticoid-mediated immunosuppression may occur at the level of the TCGF-producing cell, resulting in the control of clonal expansion of activated T cells via inhibition of TCGF production.