CD4+ T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-γ

Dominik Mumberg, Paul A. Monach, Sherry Wanderling, Mary Philip, Alicia Y. Toledano, Robert D. Schreiber, Hans Schreiber

Research output: Contribution to journalArticlepeer-review

299 Scopus citations

Abstract

CD4+ T cells can eliminate tumor cells in vivo in the absence of CD8+ T cells. We have CD4+ T cells specific for a MHC class II-restricted, tumor- specific peptide derived from a mutant ribosomal protein expressed by the UV light-induced tumor 6132A-PRO. By using neutralizing mAb specific for murine IFN-γ and adoptive transfer of CD4+ T cells into severe combined immunodeficient mice, we show that anti-IFN-γ treatment abolishes the CD4+ T cell-mediated rejection of the tumor cells in vivo. The tumor cells were MHC class II negative, and IFN-γ did not induce MHC class II expression in vitro. Therefore, the tumor-specific antigenic peptide must be presented by host cells and not the tumor cells. Tumor cells transduced to secrete IFN-γ had a markedly reduced growth rate in severe combined immunodeficient mice, but IFN-γ did not inhibit the growth of the tumor cells in vitro. Furthermore, tumor cells stably expressing a dominant-negative truncated form of the murine IFN-γ receptor α chain, and therefore insensitive to IFN-γ, nevertheless were rejected by the adoptively transferred CD4+ T cells. Thus, host cells, and not tumor cells, seem to be the target of IFN-γ. Together, these results show that CD4+ T cells can eliminate IFN-γ-insensitive, MHC class II-negative cancer cells by an indirect mechanism that depends on IFN- γ.

Original languageEnglish
Pages (from-to)8633-8638
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number15
DOIs
StatePublished - Jul 20 1999

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