Novel mechanism for inhibition of human T cells by glucocorticoids. Glucocorticoids inhibit signal transduction through IL-2 receptor
| Autor: | F Paliogianni, S S Ahuja, J P Balow, J E Balow, D T Boumpas |
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| Rok vydání: | 1993 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 151:4081-4089 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.151.8.4081 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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