CD8(-SPECIFIC TC CELLS PRIMED IN-VIVO OR IN-VITRO AGAINST THE BALB() TUMOR)C PLASMACYTOMA ADJ-PC-5 USE THE SAME TCR V-BETA FAMILIES BUT DISPLAY DISTINCT TC1 OR TC2 CHARACTERISTICS/

The involvement of counteractive CD8(+) T cell subsets in tumor-specif ic unresponsiveness was analyzed in a syngeneic murine tumor model. CD 8(+) cytotoxic T cells against the IL-10 producing BALB/c plasmacytoma ADJ-PC-5 can be easily induced in vitro, in a primary syngeneic mixed lymphocyte tumor cell culture (MLTC), or in vivo, by repeated immuniz ation of syngeneic BALB/c mice with high doses of X-irradiated ADJ-PC- 5 tumor cells. Long term cultivated CD8(+) ADJ-PC-5-specific Te lines use either TcR of the V beta 6 or V beta 8.1/8.2 type, irrespective if the lines were derived from a primary MLTC or from immunized mice. Wh ile most of the Tc lines produce type-1 cytokines (IFN-gamma, no IL-4) upon stimulation, at least two of them, which were derived from a pri mary MLTC, display a type-2 cytokine spectrum (IL-4, no IFN-gamma). Th e primary in vitro Tc response against ADJ-PC-5 cells shows characteri stics of a TC2 response: CD8(+) Tc cells which are induced in a primar y MLTC do not produce IFN-gamma, and the tumor-specific Tc response is enhanced by IL-4 but suppressed by IFN-gamma or IL-12. In contrast, A DJ-PC-5-specific CD8(+) Tc cells from immunized mice are IFN-gamma pro ducing TC1 cells. Since the primary in vitro Tc response against the t umor is suppressed even by lowest numbers of irradiated ADJ-PC-5-speci fic TC1 cells via IFN-gamma, these TC1 cells behave similar to a previ ously described regulatory subset of IFN-gamma producing CD8(+) T cell s, which are induced during early stages of ADJ-PC-5 tumorigenesis and inhibit the induction of a tumor-specific Tc response from naive BALB /c spleen cells in vitro.