Differential requirement of perforin and IFN-gamma in CD8 T cell-mediated immune responses against B16.F10 melanoma cells expressing a viral antigen
| Autor: | A, Prévost-Blondel, M, Neuenhahn, M, Rawiel, H, Pircher |
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| Rok vydání: | 2000 |
| Předmět: |
Cytotoxicity
Immunologic Pore Forming Cytotoxic Proteins Mice Inbred BALB C Lung Neoplasms Membrane Glycoproteins Perforin Melanoma Experimental Receptors Antigen T-Cell Mice Transgenic CD8-Positive T-Lymphocytes Adoptive Transfer Cell Line Interferon-gamma Mice Animals Lymphocytic choriomeningitis virus |
| Zdroj: | European journal of immunology. 30(9) |
| ISSN: | 0014-2980 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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