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International Immunology Advance Access originally published online on December 2, 2008
International Immunology 2009 21(1):53-62; doi:10.1093/intimm/dxn123
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Javier G. Casado1, Olga DelaRosa2, Graham Pawelec3, Esther Peralbo2, Esther Duran4, Fernando Barahona5, Rafael Solana2 and Raquel Tarazona1

1 Department of Physiology, Immunology Unit, Faculty of Veterinary, University of Extremadura, Caceres, Spain
2 Department of Cellular Biology, Physiology and Immunology, Faculty of Medicine, University of Cordoba, Cordoba, Spain
3 Tübingen Ageing and Tumour Immunology Group Center for Medical Research, University of Tübingen, Tübingen, Germany
4 Anatomy and Comparative Pathological Anatomy Unit, Faculty of Veterinary, University of Extremadura, Caceres, Spain
5 Centro de Biologia Molecular, University Autonoma, Madrid, Spain

Correspondence to: R. Tarazona; E-mail: rtarazon{at}unex.es

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.

Keywords: cytotoxic T cell differentiation, ELAGIGILTV peptide, melanoma, population doubling, T cell expansion

Transmitting editor: H. R. MacDonald

Received 28 November 2007, accepted 4 November 2008.


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