The immunoregulatory effects of ultraviolet exposure: early events.

Ultraviolet (UV)-irradiation of mice is known to cause a modification in their immune potential such that exposed mice lose their ability to reject transplanted UV-induced tumors. Further, this tumor susceptibility is mediated by a population of suppressor T lymphocytes (Ts) found in the spleen and lymph nodes of UV-exposed animals which will adoptively transfer tumor susceptibility to normal animals. As the induction of these Ts cells is undoubtedly a complex process, my studies were initiated to elucidate the early events involved in this process. It was found that sunscreen agents such as para-aminobenzoic acid (PABA), while able to prevent the pathological skin damage associated with the UV exposure, were without effect on the induction of tumor susceptibility. To date, however, I have been unable to detect T(,s) cells in PABA-treated UV-irradiated mice. Animals exposed to six daily UV exposures (about 3000 J/m('2)/day) have been reported to exhibit decreased antigen-presenting and accessory cell function (assayed solely from the spleen). My investigations have confirmed this finding. Further, the results demonstrated that this is: (1) probably due to UV-induced inflammation and; (2) the result of a migration of antigen-presenting cells (APC) from the spleen to the peripheral lymph nodes. These results are consistent with previous studies which found that UV-irradiation does not cause a generalized suppression in immune responses. While regional differences in APC activity may be attributable to cellular migration, a direct inactivation of epidermal Langerhans cells (the epidermal APC) also occurs (as assessed in vitro) following UV exposure. My results demonstrated that the APC function of epidermis was immediately lost in a dose-dependent manner following UV-irradiation. Further, treatment of skin with PABA prior to the UV exposure did not significantly alter the rate of Langerhans cell inactivation. Abrogation of contact sensitivity responses after a single UV exposure, however, required two to three days between exposure and sensitization. Collectively, these data indicate that early in the course of the treatments, UV-irradiation causes both a direct inactivation of epidermal APC and a migration of splenic APC to peripheral lymph nodes. Hence, these events may play a role in the cellular interactions involved in the induction of the Ts cells which mediate the UV-induced tumor susceptible state.