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 examine this issue further, we applied either high or low doses of dinitrofluorobenzene (DNFB) epicutaneously to mice. We observed reduced LC density at the site after 12 h (nadir), which returned to normal levels at 24 h only after a low dose of hapten. When a low dose of an unrelated hapten, oxazolone, was painted on skin that had been painted 12 h previously with high dose of DNFB, oxazolone-specific CH was impaired. When grafts of whole skin, dermis alone, and epidermis alone prepared from skin painted 2 h previously with low or high doses of DNFB were placed onto naive, syngeneic mice, CH was induced by whole skin after both types of doses, by epidermis only after a low dose, and by dermis only after high dose. When epidermal cell suspensions were derivatized in vitro with low or high doses of DNFB, only cells exposed to a low dose induced proliferation of hapten-specific Tcells. Thus, only a low dose of hapten reveals the APC functions of LC without the participation of dermal APC.