Characterization of a cloned ultraviolet radiation (UV)-induced suppressor T cell line that is capable of inhibiting anti-UV tumor-immune responses

Ultraviolet radiation (UV) is a potent carcinogen for the induction of skin tumors. In this regard, UV represents a unique carcinogenic agent, in that depending on the dosage and conditions of administration it can function as either a complete carcinogen, a carcinogenic promoting agent, or an immunologic modulator of anti-tumor rejection responses. The immunologic modulatory activity of UV has been demonstrated in numerous studies. These studies have shown that subcarcinogenic doses of UV induce a population of suppressor T lymphocytes (Ts cells) that allow for the emergence and progression of UV-induced tumors. Although the phenotypic and functional properties of these cells have been established, it was unclear as to whether the UV-induced Ts cell population consisted of multiple Ts cell clones able to recognize a range of unique tumor antigens or a limited number of Ts cell clones with functional specificity directed toward a common tumor-associated antigen (TAA). To address this question, an interleukin 2-dependent, UV-induced cloned Ts cell line was derived, by limiting dilution without exogenous antigen stimulation, from the splenic T cell population of a C3H mouse that had been exposed to a subcarcinogenic dose of UV. This Ts cell line, designated UV2.10, was selected for its ability to suppress the in vitro differentiation of cytotoxic T cells from the draining lymph nodes of UV-induced tumor-immune mice. When transferred into non-UV-irradiated syngeneic mice, which normally reject a UV-induced tumor implant, the UV2.10 cells rendered their hosts susceptible to the growth of a battery of UV-induced tumors. Although capable of suppressing in vitro and in vivo UV-induced tumor-immune responses, UV2.10 cells did not inhibit the elicitation of contact hypersensitivity responses, the rejection of allogeneic skin grafts, responses, the rejection of allogeneic skin grafts, or the rejection of allogeneic UV-induced tumors. These data suggest that the cloned UV2.10 Ts cell line possesses functional antigenic specificity that may be limited to the regulation of immune responses that are directed toward the TAA expressed by syngeneic UV-induced tumors. Employing monoclonal antibodies and FACS analysis, the cell surface phenotype of the UV2.10 cell line was determined to be: Thy-1.2+, Lyt-1-, Lyt-2+/- (dim), L3T4a-, I-A/E-, and I-J+. This cell surface phenotype is indicative of a suppressor T cell. These data lend further support to the hypothesis that the UV-induced Ts cell population is clonal in nature and functions through its ability to recognize a common TAA(s) that appears to be expressed by virtually all UV-induced tumors.