Correlation of effector function with phenotype and cell division after in vitro differentiation of naive MART-1-specific CD8+ T cells.
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.
Casado
Javier G
JG
Department of Physiology, Immunology Unit, Faculty of Veterinary, University of Extremadura, Caceres, Spain.
DelaRosa
Olga
O
Pawelec
Graham
G
Peralbo
Esther
E
Duran
Esther
E
Barahona
Fernando
F
Solana
Rafael
R
Tarazona
Raquel
R
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
D000951:Antigens, Neoplasm; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens