Faculty Collaboration Database

Regulatory T cell development in the absence of functional Foxp3. Nat Immunol 2007 Apr;8(4):359-68

Date

02/03/2007

Pubmed ID

17273171

DOI

10.1038/ni1445

Scopus ID

2-s2.0-33947600584 (requires institutional sign-in at Scopus site)   397 Citations

Abstract

Although the development of regulatory T cells (T(reg) cells) in the thymus is defined by expression of the lineage marker Foxp3, the precise function of Foxp3 in T(reg) cell lineage commitment is unknown. Here we examined T(reg) cell development and function in mice with a Foxp3 allele that directs expression of a nonfunctional fusion protein of Foxp3 and enhanced green fluorescent protein (Foxp3DeltaEGFP). Thymocyte development in Foxp3DeltaEGFP male mice and Foxp3DeltaEGFP/+ female mice recapitulated that of wild-type mice. Although mature EGFP(+) CD4(+) T cells from Foxp3DeltaEGFP mice lacked suppressor function, they maintained the characteristic T(reg) cell 'genetic signature' and failed to develop from EGFP(-) CD4(+) T cells when transferred into lymphopenic hosts, indicative of their common ontogeny with T(reg) cells. Our results indicate that T(reg) cell effector function but not lineage commitment requires the expression of functional Foxp3 protein.

Author List

Lin W, Haribhai D, Relland LM, Truong N, Carlson MR, Williams CB, Chatila TA

Author

Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Lineage
Female
Flow Cytometry
Forkhead Transcription Factors
Gene Expression Profiling
Green Fluorescent Proteins
Immunophenotyping
Lymphocyte Activation
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, SCID
Mutagenesis, Site-Directed
Polymerase Chain Reaction
Self Tolerance
T-Lymphocytes, Regulatory
Thymus Gland