Glucocorticoids accelerate anti-T cell receptor-induced T cell growth

G J Wiegers, M S Labeur, I E Stec, W E Klinkert, F Holsboer, J M Reul

Research output: Contribution to journalArticle (Academic Journal)peer-review

92 Citations (Scopus)

Abstract

To study steroid regulation of cell-mediated immunity, we used anti-TCR-stimulated rat splenic lymphocyte mitogenesis as our experimental paradigm. Surprisingly, we found that the principal glucocorticoid of the rat, corticosterone (CORT), potently enhanced anti-TCR-induced lymphocyte proliferation after 2 to 3 days in culture, followed by inhibited cell growth after 5 to 7 days. Thus, glucocorticoids appeared to accelerate anti-TCR-induced lymphocyte mitogenesis. This effect occurred at physiologic concentrations (50-1000 nM), which are known to be released in vivo after an immune challenge. Kinetic experiments showed that CORT had to be present within 60 min after the initiation of TCR activation to produce maximal enhancing effects; a delay of 2 h or more left CORT ineffective. The lymphocytes incubated with CORT may have an increased sensitivity to IL-2 because 1) CORT suppressed IL-2 production throughout the culture period, and 2) an anti-IL-2R mAb completely blocked both control and CORT-treated anti-TCR-induced lymphocyte proliferation. Although the IL-2R alpha- and beta-chain mRNA concentrations were not altered in CORT-treated splenocyte cultures, we observed by FACS analysis an increased expression of the IL-2R alpha-chain on CORT-treated TCR alpha beta + and CD4+ T cells after 48 to 72 h of culture, suggesting an increased sensitivity of these T cells to IL-2 during the phase of enhanced proliferation. These results demonstrate a clear distinction between the enhancing effects of glucocorticoids on anti-TCR-induced lymphocyte proliferation and their well known inhibitory actions. Thus, the present study expands the regulatory role of glucocorticoids in cellular immunity, adding a novel effective stimulatory component to their inhibitory properties.

Original languageEnglish
Pages (from-to)1893-902
Number of pages10
JournalJournal of Immunology
Volume155
Issue number4
Publication statusPublished - 15 Aug 1995

Keywords

  • Animals
  • Antibodies, Monoclonal
  • Cells, Cultured
  • Corticosterone
  • Interleukin-2
  • Lymphocyte Activation
  • Male
  • Mice
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Interleukin-2
  • T-Lymphocytes

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