Rat mammary adenocarcinoma 13762 expressing IFN-gamma elicits antitumor CD4+ MHC class II-restricted T cells that are cytolytic in vitro and tumoricidal in vivo.
Rat adenocarcinoma 13762 was modified by transfection to express IFN-gamma, and the tumor-forming potential of cytokine-producing cells was found to be dramatically impaired. Animals resistant to inocula of IFN-gamma-modified tumor were resistant to subsequent challenge with unmodified 13762 tumor. Induced immunity was tumor specific in that syngeneic but non-cross-reactive tumor grew with normal kinetics in animals injected with IFN-gamma-producing 13762 tumor. Antitumor T cells were derived from animals primed with IFN-gamma-producing 13762 tumor and expanded into a cell line by coculture in vitro with IFN-gamma-producing 13762 cells. Anti-13762-gamma T cells were cytotoxic in vitro toward IFN-gamma-producing 13762 tumor and were not reactive with other syngeneic tumors or spleen B cells. Anti-13762-gamma T cells were determined to be CD4+ by Ab staining and flow cytometric analysis, and recognition of 13762-gamma in vitro was inhibited by anti-MHC class II Ab. Anti-13762-gamma T cells were not reactive in vitro with wild-type 13762 tumor unless treated with exogenous rIFN-gamma, which induced expression of cell surface MHC class II. However, adoptively transferred anti-13762-gamma T cells could effect regression of wild-type 13762 tumor or dramatically inhibit progressive growth in animals carrying significant tumor burden, and the antitumor phenotype did not require CD8+ T cells in vivo. These experiments demonstrate that although antitumor T cells elicited against cytokine-modified tumor may fail to demonstrate reactivity with unmodified tumor in vitro, antitumor properties may be manifest in vivo.
Frey
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Department of Cell Biology, New York University School of Medicine, NY 10016, USA.
D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000276:immunology; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma