title: Correlation of effector function with phenotype and cell division after in vitro differentiation of naive MART-1-specific CD8+ T cells.
abstract: Adoptive transfer of antigen-specific CD8+ T cells may represent an effective strategy for immunotherapy of tumors such as melanoma, but is limited by the number and functionality of in vitro expanded T cells. Here, we document that although ELAGIGILTV-specific CD8+ T cells from different donors initially possessed a naive phenotype, after antigen-induced in vitro expansion two distinct phenotypes correlating with cell proliferation rate emerged in the different donors. Those cultures achieving fewer cumulative population doublings (CPDs) were cytotoxic and displayed a CD45RA+CCR7- phenotype. In contrast, cultures reaching higher CPDs were non-cytotoxic T cells with a CD45RA-CCR7- phenotype. Thus, the generation of larger numbers of ELAGIGILTV-specific CD8+ T cells correlates negatively with the acquisition of a CD45RA+CCR7- phenotype and cytotoxic capacity. A better understanding of the differentiation pathways of cytotoxic T cells to obtain optimally efficient cells for adoptive transfer will allow the development of new immunotherapy protocols.
authors.affiliation: Department of Physiology, Immunology Unit, Faculty of Veterinary, University of Extremadura, Caceres, Spain.
authors.forename: Javier G
authors.initials: JG
authors.lastname: Casado
authors.forename: Olga
authors.initials: O
authors.lastname: DelaRosa
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
authors.forename: Esther
authors.initials: E
authors.lastname: Peralbo
authors.forename: Esther
authors.initials: E
authors.lastname: Duran
authors.forename: Fernando
authors.initials: F
authors.lastname: Barahona
authors.forename: Rafael
authors.initials: R
authors.lastname: Solana
authors.forename: Raquel
authors.initials: R
authors.lastname: Tarazona
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology* / Q000378:metabolism; D058965:MART-1 Antigen; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens