title: Cutting edge: CD4+ T cell control of CD8+ T cell reactivity to a model tumor antigen.
abstract: Neoantigens resulting from the inherent genomic instability of tumor cells generally do not trigger immune recognition. Similarly, transfection of tumors with model Ags often fails to elicit CD8+ T cell responses or alter a tumor's growth rate or lethality. We report here that the adoptive transfer of activated Th1-type CD4+ T cells specific for a model tumor Ag results in the de novo generation of CD8+ T cells with specificity to that Ag and concomitant tumor destruction. The anti-tumor effects of the CD4+ T cells required the presence of both MHC class I and class II on host cells, as evidenced by experiments in knockout mice, suggesting that CD4+ T cells enhanced the ability of host APC to activate endogenous CD8+ T cells. These results indicate that the apparent inability of tumor cells expressing highly immunogenic epitopes to activate tumor-specific CD8+ T cells can be altered by activated CD4+ T cells.
authors.affiliation: Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Surman
authors.forename: M E
authors.initials: ME
authors.lastname: Dudley
authors.forename: W W
authors.initials: WW
authors.lastname: Overwijk
authors.forename: N P
authors.initials: NP
authors.lastname: Restifo
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002999:Clone Cells / Q000276:immunology / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000201:enzymology / Q000276:immunology / Q000628:therapy; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D001616:beta-Galactosidase