%0 Electronic Article %A Li, Yongqing and Yee, Cassian %I American Society of Hematology %D 2008 %D 2008 %G English %@ 0006-4971 %@ 1528-0020 %~ Universitätsbibliothek "Georgius Agricola" %T IL-21–mediated Foxp3 suppression leads to enhanced generation of antigen-specific CD8+ cytotoxic T lymphocytes %V 111 %J Blood %V 111 %N 1 %P 229-235 %U http://dx.doi.org/10.1182/blood-2007-05-089375 %X 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. %Z https://katalog.ub.tu-freiberg.de/Record/ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4Mi9ibG9vZC0yMDA3LTA1LTA4OTM3NQ %U https://katalog.ub.tu-freiberg.de/Record/ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4Mi9ibG9vZC0yMDA3LTA1LTA4OTM3NQ