Suppression of tumour-specific cytotoxic T-cell responses against the syngeneic BALB/c plasmacytoma ADJ-PC-5 by tumour-induced CD8+ regulatory T cells via IFN-gamma.

Abstract

The mechanisms of tolerance induction by tumour cells during early stages of tumourigenesis were analysed in a murine model system using the highly immunogenic BALB/c plasmacytoma ADJ-PC-5. Early stages of tumourigenesis were simulated in syngeneic BALB/c mice by repeated intraperitoneal injections with subimmunogenic doses of X-irradiated ADJ-PC-5 tumour cells. This treatment causes a state of tumour-specific tolerance in a high percentage of mice, involving a population of CD8+ peritoneal T cells which are able to suppress a protective tumour-specific Tc response against this tumour. Using a primary mixed lymphocyte tumour cell culture (MLTC) as an in vitro system to study suppressive mechanisms of such regulatory T cells, the role of production or consumption of a number of cytokines was analysed. The data presented here demonstrate that inhibition of a protective Tc response against ADJ-PC-5 tumour cells is due to IFN-gamma production by suppressive T cells from 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-induced suppressive T cells and tumour-specific Tc cells seem to represent functionally and phenotypically different subsets of CD8+ T cells, possibly pointing towards a differential activation of type-1 and type-2 CD8+ T cells depending on the dose of tumour cells.