title: Therapy with anti-TNFα antibody enhances number and function of Foxp3(+) regulatory T cells in inflammatory bowel diseases.
abstract: BACKGROUND
  Inflammatory bowel diseases (IBDs) are associated with up-regulation of TNFα, hyperactivation of proinflammatory effector T cells (Teffs) and inefficient control by regulatory CD4(+) CD25(+) Foxp3(+) T cells (Tregs). The aim of this prospective study was to investigate the short-term impact of treatment of IBD patients with anti-TNFα antibodies (infliximab or adalimumab) on the frequency, phenotype, and suppressive function of Tregs.
  
  
  METHODS
  Active IBD patients including 16 with Crohn's disease and 9 with ulcerative colitis were treated with anti-TNFα mAb. PBMCs were harvested immediately before and 2 weeks after the first injection. The frequency and phenotype of circulating CD4(+) CD25(+) Foxp3(+) Tregs were analyzed by flow cytometry, and their suppressive function was assessed by the ability of purified CD4(+) CD25(+) CD127(-) Tregs to inhibit the proliferation of allogenic CD4(+) CD25(-) Teffs.
  
  
  RESULTS
  CD4(+) CD25(+) Foxp3(+) Treg frequency was significantly lower in active IBD patients than in controls (2.8% ± 0.4% vs. 4.6% ± 0.6%, respectively; P = 0.01). On day 14 following the first anti-TNFα infusion, the frequency of circulating Tregs was significantly enhanced in IBD patients (4.0% ± 0.5% vs. 2.8% ± 0.4%, before treatment; P = 0.001), with a 2- to 3-fold increase in the intensity of Foxp3 expression. In addition, infliximab treatment enhanced the suppressive function of circulating Tregs, as shown by inhibition of Teff proliferation at a 1:8 Treg/Teff ratio (28% ± 5% vs. 66% ± 10%, after treatment; P = 0.04).
  
  
  CONCLUSIONS
  These data demonstrate that anti-TNFα treatment of active IBD rapidly enhances the frequency of functional Foxp3(+) Tregs in blood and potentiates their suppressive function. This indicates that Treg potentiation may represent an unanticipated outcome of anti-TNFα biotherapy in IBD.
authors.affiliation: INSERM U 851 Immunité et Vaccination, CERVI, IFR 128 Biosciences Lyon Gerland, Lyon, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Boschetti
authors.forename: Stéphane
authors.initials: S
authors.lastname: Nancey
authors.forename: Fatima
authors.initials: F
authors.lastname: Sardi
authors.forename: Xavier
authors.initials: X
authors.lastname: Roblin
authors.forename: Bernard
authors.initials: B
authors.lastname: Flourié
authors.forename: Dominique
authors.initials: D
authors.lastname: Kaiserlian
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab