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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2983-2990.
Prepublished online as a Blood First Edition Paper on July 20, 2007; DOI 10.1182/blood-2007-06-094656.
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IMMUNOBIOLOGY
Induction of FOXP3 expression in naive human CD4+FOXP3– T cells by T-cell receptor stimulation is transforming growth factor-ß–dependent but does not confer a regulatory phenotype
Dat Q. Tran1,
Heather Ramsey1, and
Ethan M. Shevach1
1 Laboratory of Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD
Thymic-derived natural T-regulatory cells (nTregs) are important for the induction of self-tolerance and the control of autoimmunity. Murine CD4+CD25–Foxp3– cells can be induced to express Foxp3 after T-cell receptor (TCR) activation in the presence of transforming growth factor ß (TGFß) and are phenotypically similar to nTregs. Some studies have suggested that TCR stimulation of human CD4+CD25– cells results in the induction of transient expression of FOXP3, but that the induced cells lack a regulatory phenotype. We demonstrate here that TCR stimulation alone was insufficient to induce FOXP3 expression in the absence of TGFß, whereas high levels of FOXP3 expression could be induced in the presence of TGFß. Although FOXP3 expression was stable, the TGFß-induced FOXP3+ T cells were neither anergic nor suppressive and produced high levels of effector cytokines. These results suggest that even high levels of FOXP3 expression are insufficient to define a human CD4+ T cell as a T-regulatory cell.

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