Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.
CD4+CD25+ regulatory T cells are essential for the active suppression of autoimmunity. Here we report that the forkhead transcription factor Foxp3 is specifically expressed in CD4+CD25+ regulatory T cells and is required for their development. The lethal autoimmune syndrome observed in Foxp3-mutant scurfy mice and Foxp3-null mice results from a CD4+CD25+ regulatory T cell deficiency and not from a cell-intrinsic defect of CD4+CD25- T cells. CD4+CD25+ regulatory T cells rescue disease development and preferentially expand when transferred into neonatal Foxp3-deficient mice. Furthermore, ectopic expression of Foxp3 confers suppressor function on peripheral CD4+CD25- T cells. Thus, Foxp3 is a critical regulator of CD4+CD25+ regulatory T cell development and function.
Fontenot
Jason D
JD
Howard Hughes Medical Institute, Department of Immunology, University of Washington, Box 357370, Seattle, WA 98195, USA.
Gavin
Marc A
MA
Rudensky
Alexander Y
AY
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D051858:Forkhead Transcription Factors; D018390:Gene Targeting; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015375:Receptors, Interleukin-2