Regulatory T cell development in the absence of functional Foxp3.
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.
Lin
Wen
W
Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, The David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California 90095, USA.
Haribhai
Dipica
D
Relland
Lance M
LM
Truong
Nga
N
Carlson
Marc R
MR
Williams
Calvin B
CB
Chatila
Talal A
TA
D000818:Animals; D019070:Cell Lineage; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000235:genetics; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D017634:Self Tolerance / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins