DIFFERENTIAL REGULATION OF EPIDERMAL-CELL TUMOR-ANTIGEN PRESENTATION BY IL-1-ALPHA AND IL-1-BETA

IL-1 exists in two forms, termed IL-1 alpha and IL-1 beta, which exert similar effects in a number of biologic models, Recently, there have been reports of some differences in the activities of these two specie s in some systems. To address this issue with. regard to Langerhans ce lls, Langerhans cell-enriched preparations of epidermal cells were tre ated with either IL-1 alpha or IL-1 beta before pulsing with S1509a tu mor-associated antigens and subsequent use for immunization of naive m ice to S1509a. While epidermal cells treated with 100 U IL-1 beta per ml were able to induce protective tumor immunity (as indicated by the rejection of a subsequent tumor challenge with viable S1509a tumor cel ls), epidermal cells treated with 100 U IL-1 alpha per ml failed to co nfer protective immunity. At 1000 U per ml, IL-1 beta also inhibited t he ability of epidermal cells to induce tumor immunity. To investigate the effects of the two IL-1 forms on elicitation of tumor immunity, n aive mice were immunized against the S1509a tumor by s.c. injection of dead S1509a cells, Epidermal cells enriched for Langerhans cells were treated with either 100 U IL-1 alpha or IL-1 beta per ml before tumor -associated antigens-pulsing. Epidermal cells were then washed and inj ected into a hind footpad of tumor immune mice and 24 h footpad swelli ng was assessed as a measure of delayed-type hypersensitivity. Exposur e to IL-1 alpha led to suppressed elicitation of delayed-type hypersen sitivity, whereas IL-1 beta treated epidermal cells elicited a normal (100 U per ml) or enhanced (1000 U per ml) level of delayed-type hyper sensitivity. Previous experiments indicated that the suppressive effec ts of IL-1 alpha on induction of immunity may be mediated by TNF alpha , Therefore, the ability of IL-1 alpha or IL-1 beta to induce epiderma l cell production of TNF alpha was assessed. IL-1 alpha induced epider mal cells to secrete significantly higher amounts of TNF alpha protein compared with stimulation with IL-1 beta, IL-1 alpha and IL-1 beta ap pear to differentially regulate epidermal cell antigen presenting capa bility.