Correlation of effector function with phenotype and cell division after in vitro differentiation of naive MART-1-specific CD8+ T cells

Int Immunol. 2009 Jan;21(1):53-62. doi: 10.1093/intimm/dxn123. Epub 2008 Dec 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology*
  • Cell Differentiation / immunology
  • Cell Division / immunology
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Leukocyte Common Antigens / immunology*
  • Leukocyte Common Antigens / metabolism
  • MART-1 Antigen
  • Neoplasm Proteins / immunology*
  • Peptide Fragments / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism


  • Antigens, Neoplasm
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Peptide Fragments
  • Interferon-gamma
  • Leukocyte Common Antigens