Studies on the mechanism of systemic suppression of contact hypersensitivity by ultraviolet B radiation.

Exposure of mice to ultraviolet (UV) B radiation (280-320 nm) induces suppressor T lymphocytes (Ts) that prevent the rejection of primary skin cancers. A model for understanding how UVB radiation activates the suppressor cell pathway is based on the finding that UVB irradiation of mice also induces hapten-specific Ts following application of a contact sensitizing agent to unirradiated skin. Studies presented here address the mechanism by which the Ts pathway is activated in UV-irradiated mice. The hypothesis tested is that the induction of Ts results from a direct alteration of circulating antigen-presenting cells (monocytes) by the radiation. This hypothesis predicts that the UV-induced suppression of contact hypersensitivity will be reversed by replacing the antigen-presenting cells (monocytes or macrophages) after irradiation. To test this prediction, UVB-irradiated mice were given normal bone marrow cells, spleen fragments, splenic antigen-presenting cells, or stimulants of endogenous bone marrow cells. None of these procedures reversed the effects of the irradiation. Furthermore, immunization of UVB-irradiated mice with hapten-coupled splenic macrophages also failed to restore the contact hypersensitivity reaction. Therefore, direct inactivation of circulating monocytes does not appear to be the mechanism by which UVB radiation induces Ts. Experiments are also presented indicating that passive accumulation of inflammatory cells in the skin does not explain the UVB-induced systemic suppression of contact hypersensitivity. Collectively, these results support the hypothesis that a soluble mediator, induced by exposure of the skin to UVB radiation, is involved in UVB-induced systemic immunosuppression.