B7-1 EXPRESSION OF LANGERHANS CELLS IS UP-REGULATED BY PROINFLAMMATORY CYTOKINES, AND IS DOWN-REGULATED BY INTERFERON-GAMMA OR BY INTERLEUKIN-10

Langerhans cells (LC) act as potent antigen-presenting cells (APC) for primary and secondary T cell-dependent immune responses. LC express several costimulatory and/or adhesion molecules such as B7/BB1, which has been implicated as one of the important determinants for professional APC. Recent studies have shown that B7/BB1 antigens comprise three distinct molecules termed B7-1, B7-2, and B7-3. We have examined the regulatory properties of B7-1 expression in LC using various cytokines including interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-10, interferon (IFN)-gamma, granulocyte/macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF)-alpha. We have demonstrated: 1) that the B7-1 expression of LC is reproducibly up-regulated by either GM-CSF, TNF-alpha, IL-1 alpha, IL-1 beta, or IL-4 in a dose- and time-dependent manner, 2) that GM-CSF exhibits the most active effect on B7-1 up-regulation in each experiment, 3) that IFN-gamma or IL-10 profoundly inhibits the B7-1 expression of LC in a dose- and time-dependent manner, and 4) that the down-regulatory ability of IFN-gamma or IL-10 neutralizes the activity of up-regulatory cytokines. The enhancing or inhibitory action of these cytokines on B7-1 expression occurs selectively because none of the cytokines consistently affects I-A expression of LC. These data suggest that the B7-1 expression of LC may be dynamically regulated by these up- and down-regulatory cytokines in normal and inflammatory epidermal microenvironment.