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

Eur J Immunol. 2000 Sep;30(9):2507-15. doi: 10.1002/1521-4141(200009)30:9<2507::AID-IMMU2507>3.0.CO;2-V.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Cytotoxicity, Immunologic
  • Interferon-gamma / physiology*
  • Lung Neoplasms / secondary
  • Lymphocytic choriomeningitis virus / immunology
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / secondary
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Receptors, Antigen, T-Cell / physiology

Substances

  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Receptors, Antigen, T-Cell
  • Perforin
  • Interferon-gamma