TY - JOUR
T1 - CD4+ T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-γ
AU - Mumberg, Dominik
AU - Monach, Paul A.
AU - Wanderling, Sherry
AU - Philip, Mary
AU - Toledano, Alicia Y.
AU - Schreiber, Robert D.
AU - Schreiber, Hans
PY - 1999/7/20
Y1 - 1999/7/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033587720&partnerID=8YFLogxK
U2 - 10.1073/pnas.96.15.8633
DO - 10.1073/pnas.96.15.8633
M3 - Article
C2 - 10411927
AN - SCOPUS:0033587720
SN - 0027-8424
VL - 96
SP - 8633
EP - 8638
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 15
ER -