B7‐1 expression of Langerhans cells is up‐regulated by proinflammatory cytokines, and is down‐regulated by interferon‐γ 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)‐1α, IL‐1β, IL‐2, IL‐3, IL‐4, IL‐5, IL‐6, IL‐7, IL‐10, interferon (IFN)‐γ, granulocyte/macrophage colony‐stimulating factor (GM‐CSF), and tumor necrosis factor (TNF)‐α. We have demonstrated: 1) that the B7‐1 expression of LC is reproducibly up‐regulated by either GM‐CSF, TNF‐α, IL‐1α, IL‐1β, 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‐γ 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‐γ 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.