SUPPRESSION OF TUMOR-SPECIFIC CYTOTOXIC T-CELL RESPONSES AGAINST THE SYNGENEIC BALB C PLASMACYTOMA ADJ-PC-5 BY TUMOR-INDUCED CD8(+) REGULATORY T-CELLS VIA IFN-GAMMA/

The mechanisms of tolerance induction by tumour cells during early sta ges of tumourigenesis were analysed in a murine model system using the highly immunogenic BALB/c plasmacytoma ADJ-PC-5. Early stages of tumo urigenesis were simulated in syngeneic BALB/c mice by repeated intrape ritoneal injections with subimmunogenic doses of X-irradiated ADJ-PC-5 tumour cells. This treatment causes a state of tumour-specific tolera nce in a high percentage of mice, involving a population of CD8(+) per itoneal T cells which are able to suppress a protective tumour-specifi c Tc response against this tumour. Using a primary mixed lymphocyte tu mour cell culture (MLTC) as an in vitro system to study suppressive me chanisms of such regulatory T cells, the role of production or consump tion of a number of cytokines was analysed. The data presented here de monstrate that inhibition of a protective Tc response against ADJ-PC-5 tumour cells is due to IFN-gamma production by suppressive T cells fr om tolerized mice, but not to IL-2 consumption. In contrast to typical CD8(+) Tc cells, ADJ-PC-5-specific CD8(+) Tc cells do not produce IFN -gamma and are furthermore suppressed by IFN-gamma. Thus, tumour-induc ed suppressive T cells and tumour-specific Tc cells seem to represent functionally and phenotypically different subsets of CD8(+) T cells, p ossibly pointing towards a differential activation of type-1 and type- 2 CD8(+) T cells depending on the dose of tumour cells.