Induction of tolerance via skin depleted of Langerhans cells by a chemical carcinogen.

Since treatment of mouse skin with the chemical carcinogen 7,12-dimethylbenz[alpha]anthracene (DMBA) substantially decreases the density of cutaneous Langerhans cells (LC), the immune status of mice sensitized to 2,4-dinitrofluorobenzene (DNFB) through DMBA-treated skin was investigated. Mice did not develop contact sensitivity to DNFB when applied to DMBA-treated dorsal trunk skin, whereas sensitization resulted when DNFB was applied to untreated abdominal wall skin. Mice immunized with DNFB via DMBA-treated skin did not respond to subsequent immunization through untreated dorsal trunk skin, demonstrating the generation of suppressor cells which could inhibit the activation of effector lymphocytes. Adoptively transferred spleen cells from mice immunized with DNFB through DMBA-treated skin inhibited the response of sensitized hosts, indicating the presence of efferently acting suppressor cells which could inhibit the function of effector lymphocytes. This study has demonstrated that sensitization via skin depleted of LC by chemical carcinogen treatment induces an active state of tolerance rather than immunity.