Interleukin-4 impairs granzyme-mediated cytotoxicity of Simian virus 40 large tumor antigen-specific CTL in BALB/c mice

In this report we analyzed the impact of interleukin-4 (IL-4) on tumor-associated simian virus 40 (SV40) large T-antigen (TAg)-specific CD8(+) cytotoxic T cells during rejection of syngeneic SV40 transformed mKSA tumor cells in BALB/c mice. Strikingly, challenge of naive mice with low doses of mKSA tumor cells revealed a CD8(+) T cell-dependent prolonged survival time of naive IL-4(-/-) mice. In mice immunized with SV40 TAg we observed in IL-4(-/-) mice, or in wild type mice treated with neutralizing anti-IL-4 monoclonal antibody, a strongly enhanced TAg-specific cytotoxicity of tumor associated CD8(+) T cells. The enhanced cytotoxicity in IL-4(-/-) mice was accompanied by a significant increase in the fraction of CD8(+) tumor associated T-cells expressing the cytotoxic effector molecules granzyme A and B and in granzyme B-specific enzymatic activity. The data suggest that endogenous IL-4 can suppress the generation of CD8(+) CTL expressing cytotoxic effector molecules especially when the antigen induces only a very weak CTL response.