title: Peripheral regulatory T cells and serum transforming growth factor-β: relationship with clinical response to infliximab in Crohn's disease.
abstract: BACKGROUND
  CD4(+)Foxp3(+) regulatory T cells (Treg) inhibit T-cell proliferation in vitro and are effective in suppressing colitis in mouse models. Tumor necrosis factor (TNF)-α, which is centrally involved in Crohn's disease (CD) pathogenesis, also impairs Treg function. Here we investigated the influence of anti-TNF therapy on Treg frequency and function in CD.
  
  
  METHODS
  Twenty CD patients were treated with infliximab administered at weeks 0, 2, and 6. Blood was collected immediately before the first infusion and after 10 weeks. Treg frequency was quantified by flow cytometry. Treg function was measured using a standard coculture assay. Serum levels of transforming growth factor (TGF)-β1 and interleukin (IL)-10 were measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Pretreatment Treg frequency and serum TGF-β1 levels were significantly higher in nonresponder than responder patients. Clinical improvement in 12 CD patients was associated with a significant increase of Treg frequency after 10 weeks. Treg were functionally active before and after treatment with infliximab, both in responder and nonresponder CD patients. In responder patients the restoration of Treg pool was accompanied by a parallel significant increase of serum TGF-β1 and IL-10. No significant change in the elevated Treg or serum TGF-β1 was seen in nonresponder patients.
  
  
  CONCLUSIONS
  This study suggests that there may be a relationship between numbers of Treg in the blood, serum TGF-β1, and response to infliximab; however, further prospective studies are needed.
authors.affiliation: First Department of Medicine, Centro per lo Studio e Cura delle Malattie Infiammatorie Croniche Intestinali, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy. a.disabatino@smatteo.pv.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Sabatino
authors.forename: Paolo
authors.initials: P
authors.lastname: Biancheri
authors.forename: Silvia
authors.initials: S
authors.lastname: Piconese
authors.forename: M Manuela
authors.initials: MM
authors.lastname: Rosado
authors.forename: Sandro
authors.initials: S
authors.lastname: Ardizzone
authors.forename: Laura
authors.initials: L
authors.lastname: Rovedatti
authors.forename: Cristina
authors.initials: C
authors.lastname: Ubezio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Massari
authors.forename: Gianluca M
authors.initials: GM
authors.lastname: Sampietro
authors.forename: Diego
authors.initials: D
authors.lastname: Foschi
authors.forename: Gabriele Bianchi
authors.initials: GB
authors.lastname: Porro
authors.forename: Mario P
authors.initials: MP
authors.lastname: Colombo
authors.forename: Rita
authors.initials: R
authors.lastname: Carsetti
authors.forename: Thomas T
authors.initials: TT
authors.lastname: MacDonald
authors.forename: Gino R
authors.initials: GR
authors.lastname: Corazza
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000276:immunology; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D000069285:Infliximab