DISSECTION OF ANTIGENIC AND IRRITATIVE EFFECTS OF EPICUTANEOUSLY APPLIED HAPTENS IN MICE - EVIDENCE THAT NOT THE ANTIGENIC COMPONENT BUT NONSPECIFIC PROINFLAMMATORY EFFECTS OF HAPTENS DETERMINE THE CONCENTRATION-DEPENDENT ELICITATION OF ALLERGIC CONTACT-DERMATITIS

Allergic contact dermatitis differs from most other immune reactions b y its strict dose dependence during the elicitation phase, Moreover, a lmost all known contact allergens can also induce dose-dependent irrit ative dermatitis and in general only elicit allergic contact dermatiti s in sensitized individuals when applied within a narrow dose range, T herefore, we hypothesized that elicitation of contact hypersensitivity (CHS) may require two signals, antigen-specific effector cell activat ion and a non-antigen-specific proinflammatory signal, both of which a re provided by application of a sufficient dose of hapten. To dissocia te these putative two signals, oxazolone-sensitized mice were ear chal lenged with a dose of the specific hapten which was too low to elicit CHS. At the same time, an unrelated hapten was applied in a convention al concentration to the same skin site, Whereas neither treatment alon e elicited a significant CHS response, application of both compounds t ogether resulted in a strong CHS response that was indistinguishable f rom that elicited by the full dose of the specific hapten, Upon coadmi nistration of the irrelevant hapten, allergic contact dermatitis could be elicited even when the dose of the specific hapten was further red uced by a factor of 10(3). In contrast, a dose reduction of the irrele vant hapten by a factor of two resulted in the loss of the CHS respons e, These data indicate that non-antigen-specific effects of epicutaneo usly applied haptens significantly contribute to the elicitation of CH S responses and that the capacity of the hapten to evoke this proinfla mmatory stimulus rather than its antigenicity is responsible for the s trict concentration dependence.