Cytotoxic CD4+ T cells associated with the expression of major histocompatibility complex class II antigen of mouse myeloma cells secreting interferon-gamma are cytolytic in vitro and tumoricidal in vivo.
Vaccination of mouse myeloma V(K)C(K)-gamma (I) cells secreting interferon (IFN)-gamma and expressing enhanced major histocompatibility complex (MHC) class I antigen (Ag) resulted in protective immunity that was mainly mediated by CD8+ T cells. V(K)C(K)-gamma (I/II) cells expressing both enhanced MHC class I and class II Ags were isolated from V(K)C(K)-gamma (I) cells. These V(K)C(K)-gamma (I/II) cells were used to study the relationship between IFN-gamma secretion of tumor cells, its tumorigenicity, and its induced immunity, as well as to evaluate the cellular immunocomponents mediating this immunity. Our animal studies showed that IFN-gamma secretion by V(K)C(K)-gamma (I/II) cells curtailed its tumorigenicity in syngeneic BALB/c mice and further induced protective immunity against a subsequent graft of parental V(K)C(K) tumor. This immunity is mediated by both CD4+ and CD8+ T cells. The activation of CD4+ T cells is associated with enhanced expression of MHC class II Ag of V(K)C(K)-gamma (I/II) cells. These CD4+ T cells are tumor specific and cytolytic in an MHC-restricted fashion in vitro, and are tumoricidal in a T-cell adoptive transfer experiment in vivo. Our data thus demonstrate that vaccination of genetically modified tumor cells secreting IFN-gamma may provide beneficial antitumor effects by inducing both cytolytic CD4+ and CD8+ cytotoxic T lymphocytes, provided that these tumor cells express both enhanced MHC class I and class II Ags.
Xiang
J
J
Saskatoon Cancer Center, Department of Microbiology, College of Medicine, University of Saskatchewan, Canada.
Moyana
T
T
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015197:Carcinogenicity Tests; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma