Glucocorticoids Regulate TCR-Induced Elevation of CD4: Functional Implications

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.

Rimexolone inhibits proliferation, cytokine expression and signal transduction of human CD4+ T-cells

“…Incubation with corticosterone at 10 −6 M enhanced the proliferative response and shifted the enhancement of CD4 expression to a time point about 24 h earlier, blockable by RU486. The authors also found a moderate inhibition of CD4 expression after 96-120 h which is consistent with our observations [19]. However, in further experiments they showed that the enhancing effect on proliferation during the first 48-72 h of culture was due to culture conditions [20].…”

“…In literature, there is only scattered information on how glucocorticoids affect CD4 expression. In one study the activation of T-cells was found to be associated with an increase in CD4 cell surface expression which is maximal after 72-96 h [19]. Incubation with corticosterone at 10 −6 M enhanced the proliferative response and shifted the enhancement of CD4 expression to a time point about 24 h earlier, blockable by RU486.…”

Winter day lengths enhance T lymphocyte phenotypes, inhibit cytokine responses, and attenuate behavioral symptoms of infection in laboratory rats

“…T cells expressing CD4 and CD25 were significantly upregulated in short days. Corticosterone treatment markedly enhances proliferation of CD4+CD25+ T lymphocytes in vitro (Wiegers et al, 2000), thus increased cell numbers in short day rats are consistent with short-day upregulation of HPA axis activity. CD4 +CD25+ T cells are commonly known as regulatory T cells (Tregs; Ziegler, 2006).…”

Reversible Disruption of Thymic Function by Steroid Treatment

“…These findings could reflect the ability of glucocorticoids to accelerate the TCR-mediated induction of T cell proliferation via the enhanced expression of the IL-2 receptor or other cytokine receptors (25,26). The steroid-induced up-regulation of IL-7R␣ and IL-7R expression observed in human CD4 ϩ T cells may also contribute to enhanced survival and function of helper T cells (27).…”