The Journal of Immunology, Vol 151, Issue 8 4081-4089, Copyright © 1993 by American Association of Immunologists

ARTICLES

Novel mechanism for inhibition of human T cells by glucocorticoids. Glucocorticoids inhibit signal transduction through IL-2 receptor

F Paliogianni, SS Ahuja, JP Balow, JE Balow and DT Boumpas
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.

Interaction of IL-2 with its high affinity membrane receptor complex (IL-2R) present on activated T lymphocytes induces cell proliferation and mediates effector functions. Glucocorticoids inhibit IL-2 production by inhibiting TCR-mediated signal transduction. We asked whether they also inhibit the action of IL-2 by inhibiting signal transduction through IL-2R. Human peripheral blood T cells, stimulated with PMA for 48 h (PMA blasts), were incubated with IL-2 in the presence of incremental dosages of dexamethasone (Dex; 10(-5)-10(-9) M). Dex inhibited the IL-2-dependent proliferation of PMA blasts in a dose-dependent fashion (IC50, 5 x 10(-8) M). Cell surface expression of IL-2R alpha- and beta-chains as determined by immunofluorescence analysis was not affected by Dex. In addition, Scatchard plot analysis of 125I-labeled IL-2 showed that Dex did not affect the binding of IL- 2, thus suggesting that inhibition is due to a postreceptor effect. Inhibition of T cell proliferation by Dex was associated with decreased IL-2-dependent tyrosine phosphorylation of several intracellular proteins and decreased phosphorylation of the retinoblastoma gene product Rb, a protein essential for controlling the progression of cells through the cell cycle. IL-2-dependent IL-2R alpha expression in PMA blasts and NF-kB induction in resting human T cells were also inhibited by Dex. These results demonstrate that glucocorticoids inhibit preactivated T cells by down-regulating signal transduction through IL-2R.

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