Differential modulation of B7-1 and B7-2 isoform expression on human monocytes by cytokines which influence the development of T helper cell phenotype.

The co-stimulatory molecules B7-1/B7-2 expressed on the surface of antigen-presenting cells have been suggested to influence the development of T helper 1 (Th1)-versus Th2-immune responses. These studies were conducted to elucidate the effect of immunoregulatory cytokines which influence the development of Th1/Th2 immune responses on the expression of the B7 isoforms B7-1 and B7-2 on resting and activated human monocytes and B cells. Interleukin (IL)-4 and IL-10, which induce the development of Th2 immune responses, down-regulated B7-2 and moderately up-regulated B7-1 expression on resting CD14+ monocytes in peripheral blood mononuclear cells. Interferon-gamma (IFN-gamma), which induces the development of Th1 immune responses, enhanced the expression of both B7-1 and B7-2 isoforms. Tumor necrosis factor (TNF)-alpha, which elicits both Th1- and Th2 characteristics depending on experimental conditions, down-regulated B7-2 but did not alter B7-1 expression. The effect of TNF-alpha and B7-2 expression is not mediated through endogenously produced IL-10, as addition of anti-IL-10 antibodies did not restore B7-2 expression. None of the other cytokines tested, including IL-1 alpha, IL-1 beta, IL-2, IL-5, IL-6, IL-12, granulocyte/macrophage colony-stimulating factor (GM-CSF), and transforming growth factor (TGF)-alpha, modulated the expression of B7 isoforms on resting monocytes. Lipoolysaccharide stimulation of monocytes down-regulated B7-2 and up-regulated B7-1 expression in a manner similar to IL-10. The expression of B7-1 and B7-2 on purified B cells were not altered by any of the cytokines tested, including IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IFN-gamma, TNF-alpha, TGF-alpha and GM-CSF. Taken together, our results suggest that the cytokines which induce Th1/Th2 immune responses exert differential effects on B7 isoform expression on resting monocytes but have no effect on resting or activated B cells.