Glucocorticoids regulate TCR-induced elevation of CD4: functional implications

G J Wiegers, I E Stec, W E Klinkert, J M Reul

Research output: Contribution to journalArticle (Academic Journal)

25 Citations (Scopus)

Abstract

CD4 serves as a coreceptor during Ag recognition by the TCR. This interaction results in a marked increase in the sensitivity of a T cell to Ag presented by MHC class II molecules. Here we report that activation of T cells either by plate-bound mAb (anti-TCR, anti-CD3) or soluble activators (staphylococcal enterotoxin A, Con A) is associated with an (up to 3-fold) increase in CD4 cell surface expression on CD25+ cells, which was maximal after 72-96 h. Incubation with the glucocorticoid hormone corticosterone (CORT) shifted the enhancement of CD4 expression to a point about 24 h earlier than that observed in control cultures. In parallel, the proliferative response of these CORT-treated cells was profoundly enhanced. An involvement of increased CD4 expression in this enhanced proliferative response was evidenced by the observation that T cell proliferation in CORT-treated cultures was much less sensitive to inhibition by an inhibitory, nondepleting anti-CD4 mAb than that in control cultures. TCR down-regulation was, however, not affected by CORT. Thus, based on this study and previous reports we propose that both TCR-mediated signals and glucocorticoids are important physiological regulators of CD4 expression. In addition, these findings may be of significance for the sensitivity of CD4+ cells to HIV infection upon T cell activation, as the efficacy of primary patient HIV entry depends on the level of surface CD4.

Original languageEnglish
Pages (from-to)6213-20
Number of pages8
JournalJournal of Immunology
Volume164
Issue number12
Publication statusPublished - 15 Jun 2000

Keywords

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Monoclonal
  • Antigens, CD4
  • CD4-Positive T-Lymphocytes
  • Cells, Cultured
  • Corticosterone
  • Down-Regulation
  • Lymphocyte Activation
  • Male
  • Mifepristone
  • Rats
  • Rats, Wistar
  • Receptors, Antigen, T-Cell
  • Receptors, Glucocorticoid
  • T-Lymphocytes

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