Differential Effects of Cytokines and Immunosuppressive Drugs on CD40, B7–1, and B7–2 Expression on Purified Epidermal Langerhans Cells1.

Summary Langerhans cells are MHC class II antigen-positive antigen-presenting cells in the epidermis. Recent studies have revealed that Langerhans cells express costimulatory molecules like B7–1 and B7–2 and the accessory molecule CD40. Although these molecules are important for the antigen-presenting function of Langerhans cells, little is known about the precise regulation of their expression on purified Langerhans cells. Using a panning technique, we purified epidermal Langerhans cells to around 95% purity. Freshly prepared Langerhans cells (fLC) expressed the mRNA for receptors for M-CSF (cfms), GM-CSF (GM-CSFR), and TNF-α (TNFRII). TNF-α markedly upregulated CD40 and B7–1 expression on Langerhans cells, but not B7–2 expression. GM-CSF moderately upregulated B7–1 and B7–2 expression, and slightly upregulated CD40 expression. M-CSF moderately upregulated B7–1 expression, but did not modulate CD40 or B7–2 expression. Dexamethasone (DEX) markedly inhibited CD40, B7–1, and B7–2 expression on Langerhans cells. Cyclosporin A (CsA) and FK506 slightly inhibited CD40 and B7–1 expression on Langerhans cells, but not B7–2. Furthermore, TNF-α restored the DEX-induced inhibition of CD40 expression on Langerhans cells, but not the inhibition of B7–1 or B7–2 expression. GM-CSF restored DEX-induced inhibition of CD40, B7–1, and B7–2 expression. M-CSF did not affect the DEX-induced inhibition of these molecule expres- sions. These data provide a better understanding of the role of selective cytokines and immunosupressive drugs in the modulation of the antigen-presenting capacity of Langerhans cells. [ABSTRACT FROM AUTHOR]