Class II-transfected tumor cells directly present endogenous antigen to CD4+ T cells in vitro and are APCs for tumor-encoded antigens in vivo.
We have previously demonstrated that class II-transfected tumor cells are very effective immunogens that protect against wild-type primary and metastatic tumor and, if supertransfected with genes encoding co-stimulatory molecules, are immunotherapeutic agents that successfully treat mice with established solid tumor. These results are consistent with our hypothesis that the class II-transfected tumor cells act as antigen-presenting cells (APCs) that directly activate tumor-specific CD4+ T cells; however, direct data supporting this hypothesis are lacking. In the present study, we test this hypothesis using class II-transfected tumor cells supertransfected with the hen egg lysozyme gene as a surrogate tumor antigen. In vitro antigen presentation assays demonstrate that class II-transfected tumor cells present to CD4+ T cells endogenously encoded tumor antigen, provided they do not co-express the class II-associated invariant chain. In vivo experiments using genetically marked tumor cells and host APCs demonstrate that both class II-transfected tumor cells and host cells are APCs for tumor-encoded antigens, although tumor cells appear to dominate the response. These results support the hypothesis that the immunogenicity and therapeutic value of class II-transfected tumor cells stem from their ability to function as APCs for tumor-encoded antigens and directly activate tumor-specific CD4+ T lymphocytes.
Armstrong
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Department of Biological Sciences, University of Maryland, Baltimore 21250, USA.
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D000818:Animals; D000938:Antigen-Presenting Cells; D000951:Antigens, Neoplasm / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015870:Gene Expression; D006183:H-2 Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007114:Immunization; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000235:genetics; D012513:Sarcoma, Experimental; D014162:Transfection; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D006183:H-2 Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D009113:Muramidase