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

F. Paliogianni, S. S. Ahuja, J. P. Balow, J. E. Balow, D. T. Boumpas

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

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 α- and β-chains as determined by immunofluorence 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-2Rα 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.

Original languageEnglish (US)
Pages (from-to)4081-4089
Number of pages9
JournalJournal of Immunology
Volume151
Issue number8
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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