Role of CD28/B7 costimulation in the dexamethasone-induced suppression of IFN-gamma

In vitro exposure of peripheral blood mononuclear cells (PBMC) to glucocort icoids (GC), at concentrations observed during psychologic stress, induces a shift in the human type 1/type 2 cytokine balance toward a type 2 cytokin e response. The mechanisms involved in these cytokine alterations are unkno wn but likely include modulation of regulatory cytokines or the interaction between the antigen-presenting cell (APC) and T lymphocyte or both. The CD 28/B7 costimulation pathway has been reported to modulate the type 1/type 2 cytokine balance and may contribute to the GC-associated cytokine alterati ons. Therefore, we sought to determine the effect of dexamethasone (Dex) on the expression and function of the human CD28/B7 costimulatory pathway and whether these alterations contribute to the Dex-induced type 1/type 2 cyto kine alterations. Dex inhibited the expression of both CD80 and CD86 on THP -1 cells, a human acute monocytic leukemia cell line, as determined by flow cytometry. Dex also inhibited the expression of CD28 and CTLA-4 on phytohe magglutinin (PHA)-stimulated CD3(+) T lymphocytes, which was attenuated by the addition of interleukin-12 (IL-12). Lastly, activation of CD28 with ant i-CD28 antibody attenuated the Dex-induced decrease in interferon-gamma (IF N-gamma) production by anti-CD3 antibody-stimulated PBMC. These data sugges t that Dex induces a modulation of the CD28/B7 costimulatory pathway that c ontributes to the shift in the type 1/type 2 cytokine balance toward a pred ominant type 2 cytokine response.