Sensitization through carcinogen-induced Langerhans cell-deficient skin activates specific long-lived suppressor...

Application of 2,4-dinitrofluorobenzene (DNFB) to BALB/c mouse skin depleted of epidermal Langerhans cells (LC) by the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) activated cells which suppress both contact sensitivity and antibody production when transferred into naive host mice. Tolerance was induced by a concentration of DNFB optimal for inducing contact sensitivity in solvent-treated control mice. The cellular and humoral responses of hosts to a second antigen, 2,4,6-trinitrochlorobenzene (TNCB), were unaffected by these suppressor cells, demonstrating specificity for DNFB. Suppressor cells for cellular and humoral immunity could still be demonstrated 6 months following activation, by which time some mice had died, presumably of old age. The dose responses to sensitizer for generation of cells which suppressed contact sensitivity and antibody production differed, indicating that separate populations of suppressor cells probably inhibit these responses. Hence, during cutaneous chemical carcinogenesis, depletion of LC may allow activation of specific long-lived suppressor cells capable of inhibiting cellular or humoral antitumor immune responses.