Differential effects of cytokines and immunosuppressive drugs on CD40, B7-1, and B7-2 expression on purified epidermal Langerhans cells

Langerhans cells are MHC class II antigen-positive antigen-presenting cells in the epidermis, Recent studies have revealed that Langerhans cells expre ss costimulatory molecules like B7-1 and B7-2 and the accessory molecule CD 40, Although these molecules are important for the antigen-presenting funct ion of Langerhans cells, little is known about the precise regulation of th eir 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), G MCSF (GM-CSFR), and TNF-alpha (TNFRII). TNF-alpha markedly upregulated CD40 and B7-1 expression on Langerhans cells, but not B7-2 expression, GM-CSF m oderately upregulated B7-1 and B7-2 expression, and slightly upregulated CD 40 expression. M-CSF moderately upregulated B7-1 expression, but did not mo dulate CD40 or B7-2 expression. Dexamethasone (DEX) markedly inhibited CD40 , B7-1, and B7-2 expression on Langerhans cells. Cyclosporin A (CsA) and FK 506 slightly inhibited CD40 and B7-1 expression on Langerhans cells, but no t B7-2, Furthermore, TNF-a restored the DEX-induced inhibition of CD40 expr ession or. Langerhans cells, but not the inhibition of B7-1 or B7-2 express ion. GM-CSF restored DEX-induced inhibition of CD40, B7-1, and B7-2 express ion. M-CSF did not affect the DEX-induced inhibition of these molecule expr essions, These data provide a better understanding of the role of selective cytokines and immunosupressive drugs in the modulation of the antigen-pres enting capacity of Langerhans cells.