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Inducible reprogramming of human T cells into Treg cells by a conditionally active form of FOXP3
Author(s) -
Allan Sarah E.,
SongZhao George X.,
Abraham Thomas,
McMurchy Alicia N.,
Levings Megan K.
Publication year - 2008
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200838373
Subject(s) - foxp3 , effector , biology , reprogramming , microbiology and biotechnology , regulator , phenotype , regulatory t cell , downregulation and upregulation , secretion , immunology , cell , il 2 receptor , t cell , immune system , gene , genetics , biochemistry
Abstract FOXP3 is required for the development of Treg and its expression is often used as a surrogate marker of functional suppression. However, it is now known that activated human T effector cells can also express FOXP3 without acquiring regulatory activity. To more closely examine the requirements for FOXP3 to reprogram human T cells into Treg, we developed a conditionally active form of FOXP3 and show here that full acquisition of Treg phenotype and function is strictly dependent on the amount of active FOXP3 a T cell expresses. In addition, the phenotypic and functional alterations induced by FOXP3 are only fully manifested following prolonged induction of protein activity. Induction of FOXP3 activity does not upregulate EBI3 or p35 mRNA, providing evidence that secretion of IL‐35 does not substantially contribute to the suppressive mechanism of human Treg. These data represent the first formal evidence that FOXP3 acts as a quantitative regulator rather than a simple molecular switch for Treg.