title: Regulatory T cells (CD4(+)CD25(bright)FoxP3(+)) expansion in systemic sclerosis correlates with disease activity and severity.
abstract: BACKGROUND
  The role and function of T regulatory (Treg) cells have not been fully investigated in patients with systemic sclerosis (SSc).
  
  
  METHODS
  Ten patients with SSc donated 20ml of peripheral blood. Activity (Valentini) and severity (Medsger) scores for SSc were calculated for all patients. Healthy volunteers (controls) were matched to each patient by gender and age. CD4(+) cells were separated using the MACS system. The numbers of Treg cells were estimated by flow cytometry after staining for CD4, CD25, and FoxP3 and calculated as patient-to-control ratio separately for each experiment. Correlations with activity and severity indices of the disease were performed. Twenty-four-hour production of TGF-beta and IL-10 by activated CD4(+) cells was measured by ELISA in culture supernatants.
  
  
  RESULTS
  The numbers of Treg cells, expressed as patient-to-control ratio, correlated significantly with both activity and severity indices (r=0.71, p=0.034 and r=0.67, p=0.044, respectively). ELISA-measured production of TGF-beta and IL-10 by CD4(+) cells was similar in patients and controls.
  
  
  CONCLUSIONS
  Increased numbers of Treg cells are present in patients with SSc, correlating with activity and severity of the disease. This expansion of Treg cells was not accompanied, however, by heightened TGF-beta or IL-10 production. Further studies to elaborate the causes and functional significance of Treg cell expansion in SSc are needed.
authors.affiliation: Department of Internal Medicine A, Bnai Zion Medical Center and Ruth & Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel. gslobodin@yahoo.com
authors.forename: Gleb
authors.initials: G
authors.lastname: Slobodin
authors.forename: Mohammad Sheikh
authors.initials: MS
authors.lastname: Ahmad
authors.forename: Itzhak
authors.initials: I
authors.lastname: Rosner
authors.forename: Regina
authors.initials: R
authors.lastname: Peri
authors.forename: Michael
authors.initials: M
authors.lastname: Rozenbaum
authors.forename: Aharon
authors.initials: A
authors.lastname: Kessel
authors.forename: Elias
authors.initials: E
authors.lastname: Toubi
authors.forename: Majed
authors.initials: M
authors.lastname: Odeh
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10