Although both CD80 (B7-1) and CD86 (B7-2/B70) have been recently identified in cultured human Langerhans cells (LC), little is known of the role and regulatory properties of CD80 and CD86 on human LC. We present here the results of a study comparing the expression and function of CD80 and CD86 in human LC using the T-helper type-1 cytokines IL-2 and interferon gamma (IFN)-gamma, and the T-helper type-2 cytokines IL-10, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Freshly isolated human LC expressed little CD80 and CD86 in vitro, but the expression of both molecules was rapidly induced during a 72-h incubation with cytokines and the expression of CD86 occurred much earlier and more strongly than that of CD80. The expression of both CD80 and CD86 was upregulated by GM-CSF and downregulated by IL-10, and the expression of CD86, but not that of CD80, was upregulated by both IL-4 and IFN-gamma. Finally, pretreatment of LC with GM-CSF and IFN-gamma, but not with IL-4, enhanced the alloreactive T-cell proliferation induced by the LC, and IL-10 pretreatment of LC decreased their capacity for alloreaction. These results indicate that the expression of both CD80 and CD86 on human LC may be regulated by these cytokines (IL-2, IL-4, GM-CSF, IFN-gamma and IL-10) secreted from helper T cells infiltrating into the inflammatory microenvironment.