Suprathreshold doses of hapten are required to induce both contact hypersensitivity and tolerance

Whereas both high (conventional) and low (optimal) doses of epicutaneously applied hapten induce contact hypersensitivity in normal mice, only conventional doses retain their capacity to induce contact hypersensitivity after acute, low dose ultraviolet B radiation in UVB-resistant mice. Recent evidence indicates that conventional doses of hapten as well as acute, low dose ultraviolet B radiation destroy virtually all epidermal Langerhans cells, which leads to the conclusions that (a) dermal antigen presenting cells have a prominent role to play in contact hypersensitivity induction, and that (b) Langerhans cell provide this function only in normal skin, and only if non-toxic amounts of hapten are present. We have now explored the ability of suprathreshold, threshold, and sub-threshold doses of hapten to induce tolerance when painted on or injected into normal skin or skin exposed to ultraviolet B radiation. Our results indicate that a single exposure of low dose, ultraviolet B radiation generated tolerance-promoting signals within the epidermis when a threshold dose of hapten was painted on the exposed site. By contrast, suprathreshold doses of hapten painted on skin after four consecutive daily doses of ultraviolet B radiation led to tolerance that arose exclusively from cells within the dermis. In absence of ultraviolet B radiation, epicutaneously applied hapten failed uniformly to induce tolerance, whether applied at suprathreshold, threshold or sub-threshold doses. We conclude that normal skin lacks cells with inherent tolerance-promoting capacity, but that cells of this type can emerge within either epidermis or dermis after exposure to acute, low dose ultraviolet B radiation.