EXPRESSION OF HEAT-STABLE ANTIGEN ON TUMOR-CELLS PROVIDES CO-STIMULATION FOR TUMOR-SPECIFIC T-CELL PROLIFERATION AND CYTOTOXICITY IN MICE

Heat-stable antigen (HSA/J11d/possibly homologous to CD24), a cell adh esion molecule capable of providing a co-stimulatory signal for T cell proliferation, is expressed on B cells, activated T cells, monocytes, granulocytes, Langerhans cells and thymocytes. Recent studies have de monstrated that co-stimulatory signals provided by cell adhesion molec ules such as B7-1 play an essential role in generation of an anti-tumo r immune response. To examine whether the co-stimulatory signal provid ed by HSA can induce an anti-tumor immune response, we have transfecte d HSA cDNA into the murine melanoma cell line K1735M2, and examined th e ability of this transfected cell line to induce tumor-specific T cel l responses. The results demonstrate that spleen cells from mice immun ized with HSA-transfected K1735M2 cells showed enhanced T cell prolife ration in a mixed lymphocyte tumor reaction (MLTR) assay and also demo nstrated a significant anti-tumor cytotoxicity to the parent tumor cel l (K1735M2). This anti-tumor cytolytic activity could be abrogated by pretreatment of effector cells with anti-mouse CD8 monoclonal antibody and complement. Under similar conditions, spleen cells from C3H mice immunized with vector-transfected K1735M2 cells neither actively proli ferate in an MLTR assay, nor did they exert significant cytolytic acti vity against the respective tumor cells. In summary, our study demonst rated that HSA can provide a co-stimulatory signal for the T cell immu ne response against tumor cells in a murine model.