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Blood, 1 January 2008, Vol. 111, No. 1, pp. 229-235. Prepublished online as a Blood First Edition Paper on October 5, 2007; DOI 10.1182/blood-2007-05-089375. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-05-089375v1 111/1/229    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Li, Y. Articles by Yee, C. Search for Related Content PubMed PubMed Citation Articles by Li, Y. Articles by Yee, C. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY IL-21–mediated Foxp3 suppression leads to enhanced generation of antigen-specific CD8+ cytotoxic T lymphocytes Yongqing Li1, and Cassian Yee1,2 1 Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; 2 Division of Oncology, Department of Medicine, University of Washington Medical Center, Seattle Efforts to reproducibly isolate tumor antigen–specific T cells from patients would be facilitated by removing immunoregulatory barriers. Using a human model for eliciting T-cell responses to tumor-associated antigens, we develop a novel strategy that eliminates nearly all Foxp3-expressing cells through the combination of CD25 depletion and IL-21 treatment resulting in a more than 150-fold decrease in Foxp3+ cells to virtually undetectable levels and a more than 200-fold increase in antigen-specific cytotoxic T lymphocytes (CTLs). The extent of Foxp3 elimination and degree of expansion of antigen-specific CTLs shown in this study have not previously been achievable and are unique to IL-21. We demonstrate for the first time a possible mechanism for IL-21–mediated expansion of antigen-specific CTLs that involves suppression of Foxp3-expressing cells and reversal of inhibition to tumor-associated antigen–specific CTL generation in vitro. Taken together, the combination of CD25 depletion and IL-21 exposure, by releasing regulatory constraints, leads to markedly enhanced CTL induction and represents a robust strategy for the ex vivo generation of antigen-specific T cells for adoptive cellular therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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