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 representan effective strategy for immunotherapy of tumors such as melanoma,but is limited by the number and functionality of in vitro expandedT cells. Here, we document that although ELAGIGILTV-specificCD8⁺ T cells from different donors initially possessed a naivephenotype, after antigen-induced in vitro expansion two distinctphenotypes correlating with cell proliferation rate emergedin the different donors. Those cultures achieving fewer cumulativepopulation doublings (CPDs) were cytotoxic and displayed a CD45RA⁺CCR7^–phenotype. In contrast, cultures reaching higher CPDs were non-cytotoxicT cells with a CD45RA^–CCR7^– phenotype. Thus, thegeneration of larger numbers of ELAGIGILTV-specific CD8⁺ T cellscorrelates negatively with the acquisition of a CD45RA⁺CCR7^–phenotype and cytotoxic capacity. A better understanding ofthe differentiation pathways of cytotoxic T cells to obtainoptimally efficient cells for adoptive transfer will allow thedevelopment of new immunotherapy protocols.