title: Deficient CD4+ CD25+ FOXP3+ T regulatory cells in acquired aplastic anemia.
abstract: Regulatory T cells are believed to control the development and progression of autoimmunity by suppressing autoreactive T cells. Decreased numbers of CD4(+)CD25(+) FOXP3(+) T cells (Tregs) are associated with impaired immune homeostasis and development of autoimmune diseases. The transcription factors FOXP3 and NFAT1 have key roles in regulatory T-cell development and function. We show that Tregs are decreased at presentation in almost all patients with aplastic anemia; FOXP3 protein and mRNA levels also are significantly lower in patients with aplastic anemia and NFAT1 protein levels are decreased or absent. Transfection of FOXP3-deficient CD4(+)CD25(+) T cells from patients with a plasmid encoding wild-type NFAT1 resulted in increased FOXP3 expression in these cells. By NFAT1 knockdown in CD4(+)CD25(+) T cells, FOXP3 expression was decreased when NFAT1 expression was decreased. Our findings indicate that decreased NFAT1 could explain low FOXP3 expression and diminished Treg frequency in aplastic anemia. Treg defects are now implicated in autoimmune marrow failure.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. solomoue@nhlbi.nih.gov
authors.forename: Elena E
authors.initials: EE
authors.lastname: Solomou
authors.forename: Katayoun
authors.initials: K
authors.lastname: Rezvani
authors.forename: Stephan
authors.initials: S
authors.lastname: Mielke
authors.forename: Daniela
authors.initials: D
authors.lastname: Malide
authors.forename: Keyvan
authors.initials: K
authors.lastname: Keyvanfar
authors.forename: Valeria
authors.initials: V
authors.lastname: Visconte
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kajigaya
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015551:Autoimmunity / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D050778:NFATC Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014162:Transfection
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human