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/
Hg. Pauels et al., 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/, Scandinavian journal of immunology, 43(4), 1996, pp. 421-430
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.