Mechanisms in the suppression of tumor rejection produced in mice by repeated UV irradiation.

Abstract

Mice exposed repeatedly to UVB (280 to 320 nm) radiation are unable to reject highly antigenic UVB-induced skin cancers, and their lymphoid organs contain T lymphocytes that transfer this inability to nonimmune recipients. We show that the phenotype of the cells capable of transferring suppression of tumor rejection is Lyt-1+2-,Ia-. Removal of the suppressive activity of spleen cells from UVB-irradiated mice through the use of monoclonal anti-Lyt-1 antibodies resulted in a population of cells capable of mediating tumor rejection when injected into lethally x-irradiated recipients. This finding demonstrates that the inability of UVB-irradiated mice to reject skin cancers induced by UVB radiation is not due to clonal deletion, e.g., the absence of lymphocytes that are capable of recognizing and responding to antigens on these tumors, but instead is likely to depend solely on the activity of suppressor lymphocytes. The phenotype of antigen-specific suppressor lymphocytes induced by painting oxazalone on the unirradiated skin of mice exposed once to UVB radiation was Lyt-1+2-, also a finding consistent with the hypothesis that the two forms of UVB-induced immunosuppression occur by means of the same mechanism. The phenotype of suppressor cells induced in mice treated once with 8-methoxypsoralen plus UVA (320 to 400 nm) radiation, followed by painting unexposed skin with oxazalone, was Lyt-1+2+, suggesting that this treatment may activate a different suppressor pathway.