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

In the murine kidney sarcoma, vaccination with the tumor-specific large T a ntigen 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 de termine whether or not the tumor is successfully rejected. By intracytoplas mic staining of CD4(+) cells, IFN gamma-producing (Th1), IL-4-producing (Th 2), and IL-10-expressing cells could be identified in vaccinated and non-va ccinated animals responding to tumor growth. Vaccinated mice rejecting the tumor showed an increase in the percentage of IL-4-producing (Th2) cells, I n contrast, in non-vaccinated mice succumbing to the tumor, the immunosuppr essive IL-10-producing cells became more abundant and the frequency of IFN gamma-expressing cells dropped at later time points. Yet, dominance by eith er a Th1 or a Th2 response could not be observed, To further clarify the re levance of these subsets, Th1 cells were enriched by cell sorting according to IFN gamma surface expression. Enriched Th1 and depleted cells, mainly c onsisting of the Th2 phenotype, were transferred together with CD8(+) T cel ls. Surprisingly, immunity could be transferred either with Th1 or Th2 cell s, 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. O ur findings support the view that the Th1/Th2 dichotomy is not central in T -cell-mediated tumor rejection. (C) 2000 Wiley-Liss, Inc.