title: FOXP3+ regulatory T cells in autoimmune hepatitis are fully functional and not reduced in frequency.
abstract: OBJECTIVE
  The pathogenesis of autoimmune hepatitis (AIH) is not understood, but it was suggested that AIH may be related to a numerical or functional impairment of CD4+CD25+FOXP3+ regulatory T cells (Treg), which are important mediators of immune tolerance to self-antigens. However, the role of Treg in AIH is not clear, since earlier studies reporting Treg impairment had used only CD25 as marker that cannot unambiguously distinguish Treg from activated effector T cells.
  
  
  METHODS
  We assessed the frequency and suppressor function of Treg using current staining protocols that can distinguish Treg from activated effector T cells.
  
  
  RESULTS
  The frequency of CD4+CD25(high)CD127(low)FOXP3+ Treg cells in blood of AIH patients was not reduced compared to healthy subjects, as shown by flow cytometry and confirmed by quantifying Treg-specific demethylation of the FOXP3 gene. Moreover, the suppressor function of Treg isolated from AIH patients was similar to that of Treg isolated from healthy subjects, indicating that Treg function was not impaired in AIH patients. However, we observed that the Treg frequency was significantly higher in those AIH patients with active disease than in those who were in a state of remission, suggesting that the Treg frequency may increase with the degree of inflammation. Indeed, analysis of FOXP3+ Treg in liver histology revealed that the intrahepatic Treg frequency was higher in AIH patients than in NASH patients and correlated with the inflammatory activity of the liver.
  
  
  CONCLUSIONS
  The frequency and function of circulating Treg cells is not impaired in AIH.
authors.affiliation: Department of Medicine I, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Peiseler
authors.forename: Marcial
authors.initials: M
authors.lastname: Sebode
authors.forename: Björn
authors.initials: B
authors.lastname: Franke
authors.forename: Frederike
authors.initials: F
authors.lastname: Wortmann
authors.forename: Dorothee
authors.initials: D
authors.lastname: Schwinge
authors.forename: Alexander
authors.initials: A
authors.lastname: Quaas
authors.forename: Udo
authors.initials: U
authors.lastname: Baron
authors.forename: Sven
authors.initials: S
authors.lastname: Olek
authors.forename: Christiane
authors.initials: C
authors.lastname: Wiegard
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
authors.forename: Christina
authors.initials: C
authors.lastname: Weiler-Normann
authors.forename: Christoph
authors.initials: C
authors.lastname: Schramm
authors.forename: Johannes
authors.initials: J
authors.lastname: Herkel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D019693:Hepatitis, Autoimmune / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit