Journal
HUMAN IMMUNOLOGY
Volume 73, Issue 3, Pages 223-231Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.humimm.2011.12.017
Keywords
FoxP3; Regulatory T cells; Human; Proliferation rate; Cell density
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Funding
- Marie Curie Intra European Fellowship [FP7-people-IEF-2008-235993]
- St. Mark's Hospital Foundation
- Brigid Balfour Fund
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T-cell proliferation rates in vitro depend on factors including initial T-cell number, dose of stimulus, culture time, and available physical space. The role of forkhead box P3 (FoxP3) in the identification of T cells with a regulatory phenotype remains controversial in humans. Through 5-carboxyfluorescein diacetate succinimidyl ester labeling of human T cells and subsequent culture of different numbers. of T cells and antigen-presenting cells (APC), we studied proliferative T-cell responses and FoxP3 expression in divided T cells. T-cell proliferation rates depended on initial T-cell/APC numbers. Proliferation rates decreased when high initial T-cell numbers were increased. FoxP3 expression was expressed exclusively in virtually all divided T cells cultured at high T-cell densities, irrespective of their CD4 nature or cytokine content, and was coexpressed with T-bet. However, when T cells were cultured on larger surfaces or at lower initial numbers, FoxP3 expression was not induced in divided T cells, even when most of the cells had undergone cell division. FoxP3(+) T cells generated at high cell densities did not elicit a suppressive phenotype and FoxP3 expression was subsequently lost in time when the stimulus was removed. Therefore, caution should be observed in the use of FoxP3 expression to identify regulatory T cells in humans because its expression may be only a consequence of activation status in a restricted environment. Crown copyright (C) 2012 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics. All rights reserved.
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