Differential requirement of perforin and IFN-γ in CD8 T cell-mediated immune responses against B16.F10 melanoma cells expressing a viral antigen

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Abstract
Perforin‐mediated lysis and secretion of IFN‐γ belong to the key effector functions of CD8 T cells. To compare the anti‐tumor activity of these two mechanisms, we used B16.F10 melanoma cells (B16GP33) expressing the cytotoxic T cell epitope GP33 and T cell receptor transgenic (TCR‐tg) mice specific for GP33 and deficient in perforin or IFN‐γ. B16GP33 tumor cells, injected either i. v. to induce experimental metastases or s. c., were similarly controlled in both wild‐type and perforin‐deficient, but not in IFN‐γ‐deficient TCR‐tg mice. A similar result was obtained when the therapeutic efficacy of adoptively transferred TCR‐tg effector cells from these mice was examined in the corresponding perforin‐ or IFN‐γ‐deficient C57BL / 6 hosts. Criss‐cross experiments further revealed that IFN‐γ production by the host strongly influenced the efficiency of the adoptively transferred effector cells. In contrast to the potent ability of GP33‐specific effector cells to mediate B16GP33 tumor regression without perforin, GP33‐specific memory cells, induced with recombinant vaccinia virus expressing GP33, failed to control B16GP33 tumor growth in the absence of perforin. In conclusion, our data demonstrate a crucial role for IFN‐γ in B16GP33 tumor cell elimination in vivo and indicate a differential requirement of perforin by effector versus memory CD8 T cells in anti‐tumor immunity.

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