The majority of ultraviolet (UV) radiation-induced tumors are rejected when transplanted into normal syngeneic hosts. This normal tumor immune response can be inhibited by suppressor T cells (Ts cells) that arise in UV-exposed animals prior to tumor emergence. These UV-induced Ts cells appear to function by an associative control mechanism, since they block immune responses to highly immunogenic, tumor-specific transplantation antigens through recognition of relatively minor common antigenic determinants. Thus, the UV-tumor system is an ideal experimental model for studying the effects of a defined immunoregulatory mechanism on tumor development. A cloned Ts-cell line, UVl, with in vivo function was derived from a UV-treated mouse. Normal syngeneic animals are rendered susceptible to the growth of UV-tumors after a single iv injection of 1x10?6? UVl cells. UVl cells also inhibit the in vitro generation of UV-tumor-specific cytotoxic T cells. This cell line provides the means to dissect UV-induced Ts-cell function using in vivo and in vitro assays. The objectives of the experiments are to: (1) establish a library of cloned UV-induced Ts-cell lines; (2) correlate the phenotypic characteristics and functional properties of these lines with those of the UV-induced Ts-cell population; and (3) define UV-induced immunoregulatory circuits using these cloned Ts-cell lines. Experiments are designed to: (1) evaluate Ts-cell line tissue culture supernatants for suppressor factors; (2) identify cellular interactions required for cloned Ts cells to mediate their suppressive effect; (3) determine if the suppression mediated by these cells is through a natural killer cell mechanism; and (4) characterize the antigenic specificities of the cell lines. The development of these lines is especially important for future investigations aimed at questions that cannot be readily addressed using heterogenous lymphoid cell populations from UV-exposed animals. (SR)
Hong, S R; Roberts, L K (1987) Cross-reactive tumor antigens in the skin of mice exposed to subcarcinogenic doses of ultraviolet radiation. J Invest Dermatol 88:154-60 |
Roberts, L K; Samlowski, W E; Daynes, R A (1986) Immunological consequences of ultraviolet radiation exposure. Photodermatol 3:284-97 |
Roberts, L K (1986) Characterization of a cloned ultraviolet radiation (UV)-induced suppressor T cell line that is capable of inhibiting anti-UV tumor-immune responses. J Immunol 136:1908-16 |