MODULATION OF T-CELL PRODUCTION OF INTERFERON-GAMMA BY HUMAN MONOCYTES - EFFECT OF ENGAGEMENT OF CD14 ON MONOCYTES

It has been suggested that CD14 might have influences on a variety of immunoregulatory functions of monocytes. The current studies therefore examined in detail the immunoregulatory roles of CD14 by studying the effects of anti-CD14 mAb. Anti-CD14 mAb suppressed the monocyte-dependent interferon-γ (IFN-γ) production by CD4+ T cells induced by soluble anti-CD3. Although anti-CD14 mAb also suppressed the IL-6 production by monocytes, the inhibition of the IFN-γ production induced by soluble anti-CD3 was not restored by addition of exogenous IL-6 or factors generated from cultured monocytes. Of note, anti-CD14 mAb decreased the expression of CD54, but not that of CD11a or CD18, on monocytes, suggesting that inhibition of the soluble anti-CD3-induced IFN-γ production by anti-CD14 mAb might be a result from decrease in CD11a/CD18-CD54-mediated interactions between CD4+ T cells and monocytes. By contrast, anti-CD14 mAb enhanced the IFN-γ production by immobilized anti-CD3-activated CD4+ T cells in the presence of monocytes. This enhancement of the IFN-γ production required physical contact between monocytes and T cells, which does not involve MHC class II antigen-CD4 interactions. These results indicate that CD14 on monocytes plays a variety of immunomodulatory functions depending upon the nature of stimulation. The data thus demonstrated the presence of several different interactions between monocytes and T cells that regulate the T cell cytokine production. © 1993 Academic Press, Inc.