title: Redundancy of direct priming and cross-priming in tumor-specific CD8+ T cell responses.
abstract: Against a subset of human cancers, vigorous tumor-specific CD8+ T cell responses can develop either spontaneously or upon allogeneic transplantation. However, the parameters that determine the induction of such pronounced anti-tumor immunity remain ill defined. To dissect the conditions required for the induction of high magnitude T cell responses, we have developed a murine model system in which tumor-specific T cell responses can be monitored directly ex vivo by MHC tetramer technology. In this model, tumor challenge of naive mice with Ag-bearing tumor cells results in a massive Ag-specific T cell response, followed by CD8+ T cell-dependent tumor rejection. We have subsequently used this model to assess the contribution of direct priming and cross-priming in the induction of tumor immunity in a well-defined system. Our results indicate that direct priming of T cells and Ag cross-priming are redundant mechanisms for the induction of tumor-specific T cell immunity. Moreover, T cell responses that arise as a consequence of Ag cross-presentation can occur in the absence of CD4+ T cell help and are remarkably robust.
authors.affiliation: Department of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Wolkers
authors.forename: G
authors.initials: G
authors.lastname: Stoetter
authors.forename: F A
authors.initials: FA
authors.lastname: Vyth-Dreese
authors.forename: T N
authors.initials: TN
authors.lastname: Schumacher
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D018106:CD28 Antigens / Q000502:physiology; D002455:Cell Division; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D018106:CD28 Antigens; D015395:Histocompatibility Antigens Class I