HIGH AND LOW-DOSES OF HAPTENS DICTATE WHETHER DERMAL OR EPIDERMAL ANTIGEN-PRESENTING CELLS PROMOTE CONTACT HYPERSENSITIVITY

In the induction of contact hypersensitivity (CH) to an epicutaneously applied hapten, we have previously proposed that low doses of hapten sensitize primarily through epidermal Langerhans' cells (LC), whereas high doses rely largely on dermal antigen-presenting cells (APC). To e xamine this issue further, we applied either high or low doses of dini trofluorobenzene (DNFB) epicutaneously to mice. We observed reduced LC density at the site after 12 h (nadir), which returned to normal leve ls at 24 h only after a low dose of hapten. When a low dose of an unre lated hapten, oxazolone, was painted on skin that had been painted 12 h previously with high dose of DNFB, oxazolone-specific CH was impaire d. When grafts of whole skin, dermis alone, and epidermis alone prepar ed from skin painted 2 h previously with low or high doses of DNFB wer e placed onto naive, syngeneic mice, CH was induced by whole skin afte r both types of doses, by epidermis only after a low dose, and by derm is only after high dose. When epidermal cell suspensions were derivati zed in vitro with low or high doses of DNFB, only cells exposed to a l ow dose induced proliferation of hapten-specific T cells. Thus, only a low dose of hapten reveals the APC functions of LC without the partic ipation of dermal APC.