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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-11-3577. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-11-3577v1 101/11/4260    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Geginat, J. Articles by Sallusto, F. Search for Related Content PubMed PubMed Citation Articles by Geginat, J. Articles by Sallusto, F. Related Collections Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2003, Vol. 101, No. 11, pp. 4260-4266 CHEMOKINES Proliferation and differentiation potential of human CD8+ memory T-cell subsets in response to antigen or homeostatic cytokines Jens Geginat, Antonio Lanzavecchia, and Federica Sallusto From the Institute for Research in Biomedicine, Bellinzona, Switzerland. Four human CD8+ T-cell subsets, naive (CCR7+CD45RA+), central memory (TCM, CCR7+CD45RA–), effector memory (TEM, CCR7–CD45RA–), and CD45RA+ effector memory cells (TEMRA, CCR7–CD45RA+) were compared for their capacity to proliferate and differentiate in response to antigen or homeostatic cytokines. Cytokine responsiveness and interleukin-15 receptor expression were low in naive T cells and progressively increased from TCM to TEM and TEMRA. In contrast, the capacity to accumulate in response to T-cell receptor (TCR) or cytokine stimulation showed a reciprocal pattern and was associated with resistance to cell death and Bcl-2 expression. Whereas all TCR-stimulated cells acquired a CD45RA–CCR7– phenotype, cytokine-stimulated cells maintained their phenotype with the exception of TCM cells, which expressed CCR7, CD45RA, and perforin in various combinations. Single CD8+ TCM cells, but not TEM cells, could be expanded with cytokines, and the obtained clones displayed several distinct phenotypes, suggesting that TCM cells are heterogeneous. Consistently, CCR4 expression in the CD8+ TCM pool discriminated CCR4+ type 2 polarized cells (Tc2) and CCR4–CTL precursors. Finally, ex vivo bromodeoxyuridine (BrdU) incorporation experiments revealed that memory subsets have different in vivo proliferation rates, with CCR4–TCM having the highest turnover and TEMRA the lowest. These results show that human CD8+ memory T-cell subsets have different proliferation and differentiation potentials in vitro and in vivo. Furthermore, they suggest that TEMRA cells are generated from a TCM subset upon homeostatic proliferation in the absence of antigen. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Zappasodi, M. Di Nicola, C. Carlo-Stella, R. Mortarini, A. Molla, C. Vegetti, S. Albani, A. Anichini, and A. M. Gianni The effect of artificial antigen-presenting cells with preclustered anti-CD28/-CD3/-LFA-1 monoclonal antibodies on the induction of ex vivo expansion of functional human antitumor T cells Haematologica, October 1, 2008; 93(10): 1523 - 1534. [Abstract] [Full Text] [PDF] A. Serra, S. Nuti, S. Tavarini, C. Sammicheli, D. Rosa, G. Saletti, E. Soldaini, S. Abrignani, and A. 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