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.