Transfer of IFNgamma-depleted CD4(+) T cells together with CD8(+) T cells leads to rejection of murine kidney sarcoma in mice

Abstract

In the murine kidney sarcoma, vaccination with the tumor-specific large T antigen induces protective immunity against the tumor. Immunity is dependent both on CD8(+) cytotoxic T cells and on CD4(+) T-helper cells. We analyzed whether the cytokine phenotype of induced CD4(+) T-effector cells might determine whether or not the tumor is successfully rejected. By intracytoplasmic staining of CD4(+) cells, IFNgamma-producing (Th1), IL-4-producing (Th2), and IL-10-expressing cells could be identified in vaccinated and non-vaccinated animals responding to tumor growth. Vaccinated mice rejecting the tumor showed an increase in the percentage of IL-4-producing (Th2) cells. In contrast, in non-vaccinated mice succumbing to the tumor, the immunosuppressive IL-10-producing cells became more abundant and the frequency of IFNgamma-expressing cells dropped at later time points. Yet, dominance by either a Th1 or a Th2 response could not be observed. To further clarify the relevance of these subsets, Th1 cells were enriched by cell sorting according to IFNgamma surface expression. Enriched Th1 and depleted cells, mainly consisting of the Th2 phenotype, were transferred together with CD8(+) T cells. Surprisingly, immunity could be transferred either with Th1 or Th2 cells, but Th2 cells were slightly more efficient. This suggests that, at least in the effector phase, a Th1 phenotype is not crucial for the rejection. Our findings support the view that the Th1/Th2 dichotomy is not central in T-cell-mediated tumor rejection.