AbstractCD80(B7‐1) and CD86(B7‐2) co‐stimulatory molecules have been reported to activate Th1/Th2 development pathways differentially. It is well known that Langerhans cells (LC), potent antigen‐presenting dendritic cells in the epidermis, express several co‐stimulatory molecules and that this expression is modulated by several cytokines. Based on the recently reported effect of interferon (IFN)‐γ and interleukin (IL)‐10 on the expression of CD80 and CD86 by LC, we examined the effects of these cytokines on the expression of CD54 (intercellular adhesion molecule‐1) and CD40 in addition to CD80 and CD86 on LC, and correlated the expression of each co‐stimulatory molecule with antigen presentation for a Th1 clone by cultured LC (cLC) treated with these cytokines. LC cultured for 72 h significantly up‐regulated MHC class II antigen expression and all the co‐stimulatory molecules we examined. As previously reported, IL‐10 or IFN‐γ inhibited the up‐regulation of CD80 expression. Granulocyte/macrophage‐colony‐stimulating factor (GM‐CSF) partially restored the suppression of CD80 expression induced by IFN‐γ on cultured LC, while it had virtually no effect on the inhibition induced by IL‐10. Antigen presentation for the myoglobin‐specific syngeneic Th1 clone by cLC, which were pre‐incubated with these cytokines, correlated well with their CD80 expression. In addition, among the antibodies for CD80, CD86, CD28 or CD40, the suppression of the Th1 clone stimulation by LC was found to occur only with anti‐CD80 and anti‐CD28 antibodies. Finally, we studied the effects of IFN‐γ and IL‐10 on GM‐CSF production by epidermal keratinocytes (KC). We could show that only IFN‐γ, but not IL‐10, suppressed GM‐CSF production by KC. These findings suggest that both IFN‐γ and IL‐10 suppress antigen presentation by LC for Th1 cells by suppressing their CD80 expression. The inhibitory effect of IFN‐γ on CD80 expression on LC appears to be partially mediated through the suppression of GM‐CSF production by KC.