Cutting edge: CD8+ effector T cells reject tumors by direct antigen recognition but indirect action on host cells.
CD8(+) effector T cells recognize malignant cells by monitoring their surface for the presence of tumor-derived peptides bound to MHC class I molecules. In addition, tumor-derived Ags can be cross-presented to CD8(+) effector T cells by APCs. IFN-gamma production by CD8(+) T cells is often critical for tumor rejection. However, it remained unclear whether 1) CD8(+) T cells secrete IFN-gamma in response to Ag recognition on tumor cells or APCs and 2) whether IFN-gamma mediates its antitumor effect by acting on host or tumor cells. We show in this study that CD8(+) effector T cells can reject tumors in bone marrow-chimeric mice incapable of cross-presenting Ag by bone marrow-derived APCs and that tumor rejection required host cells to express IFN-gammaR. Together, CD8(+) effector T cells recognize Ag directly on tumor cells, and this recognition is sufficient to reject tumors by IFN-gamma acting on host cells.
Schüler
Thomas
T
Max Delbrück Center for Molecular Medicine, Berlin, Germany. T.Schueler@dkfz-heidelberg.de
Blankenstein
Thomas
T
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D006084:Graft Rejection / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D017471:Receptors, Interferon / Q000096:biosynthesis / Q000502:physiology; D014407:Tumor Cells, Cultured; D000096743:Interferon gamma Receptor
D000951:Antigens, Neoplasm; D007371:Interferon-gamma; D010047:Ovalbumin; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor