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)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R23)
Project #
5R23CA034302-03
Application #
3446470
Study Section
Immunobiology Study Section (IMB)
Project Start
1984-02-03
Project End
1987-01-31
Budget Start
1986-02-01
Budget End
1987-01-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112