COMPARISON OF EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA AND CYCLOSPORINE-A ON ANTIGEN-PRESENTING CELLS OF BLOOD AND EPIDERMIS

The antigen-processing and -presenting functions of freshly obtained epidermal Langerhans cells (fresh LC) and 72-h cultured Langerhans cells (cultured LC) differ remarkably. It has been proposed that the disparate functional programs revealed in vitro may correspond directly with distinct in vivo physiologic functions - fresh LC are the in vitro equivalent of intraepidermal LC and cultured LC are equivalent to LC that have migrated from skin to the draining lymph node. As an approach to studying this proposal, we have compared the effects of two immunosuppressive agents, cyclosporin A (CsA) and transforming growth factor-beta (TGF-beta), on the alloantigen-presenting capabilities of fresh LC, cultured LC, and peripheral blood mononuclear cells (PBMC). CsA pretreatment (1 and 10-mu/ml x 2 h) profoundly inhibited alloantigen presentation by fresh LC, cultured LC, and PBMC. By contrast, TGF-beta pretreatment (1 and 10 ng/ml x 2 h) inhibited presentation by PBMC and cultured LC, but not by fresh LC. The resistance of fresh LC to the deleterious effects of TGF-beta is discussed in terms of the possibility that TGF-beta may inhibit antigen processing following conventional endocytosis. We suggest that fresh, but not cultured, LC escape TGF-beta effects because they possess an "alternative" endocytic pathway, marked by the presence of Birbeck granules.