TY - JOUR
T1 - Inducible reprogramming of human T cells into Treg cells by a conditionally active form of FOXP3
AU - Allan, Sarah E.
AU - Song-Zhao, George X.
AU - Abraham, Thomas
AU - McMurchy, Alicia N.
AU - Levings, Megan K.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=59749103715&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59749103715&partnerID=8YFLogxK
U2 - 10.1002/eji.200838373
DO - 10.1002/eji.200838373
M3 - Article
C2 - 19039775
AN - SCOPUS:59749103715
SN - 0014-2980
VL - 38
SP - 3282
EP - 3289
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 12
ER -