Differential requirement of perforin and IFN-gamma in CD8 T cell-mediated immune responses against B16.F10 melanoma cells expressing a viral antigen.
Perforin-mediated lysis and secretion of IFN-gamma 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-gamma. 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-gamma-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-gamma-deficient C57BL/6 hosts. Criss-cross experiments further revealed that IFN-gamma 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-gamma 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.
Prévost-Blondel
A
A
Institute of Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Germany.
Neuenhahn
M
M
Rawiel
M
M
Pircher
H
H
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D007371:Interferon-gamma / Q000502:physiology*; D008175:Lung Neoplasms / Q000556:secondary; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000556:secondary; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011948:Receptors, Antigen, T-Cell / Q000502:physiology
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011948:Receptors, Antigen, T-Cell; D054353:Perforin; D007371:Interferon-gamma