title: Restoration of Foxp3+ Regulatory T-cell Subsets and Foxp3- Type 1 Regulatory-like T Cells in Inflammatory Bowel Diseases During Anti-tumor Necrosis Factor Therapy.
abstract: BACKGROUND
  A defect in regulatory T cells (Tregs) may be involved in the pathogenesis of inflammatory bowel diseases (IBD). Several subsets of human Foxp3+ Tregs (activated and resting Tregs) have now been identified, as well as an IL-10 and IFN-γ double producing Foxp3 type 1 regulatory-like T cell (Tr1L). We have quantified these Tregs in patients with active IBD and during therapy with infliximab (IFX).
  
  
  METHODS
  Blood samples were obtained from healthy controls (n = 54) and patients with active IBD, either before (n = 62) or during IFX therapy (n = 75). Tregs were identified by immunofluorescent staining and flow cytometry analysis. Resting and activated Foxp3+ Tregs can be differentiated from Foxp3+ effector T cells (Foxp3+ Teff) by the expression of CD45RA. Tr1L are identified as CD4+CD45RA-CD25-CD127-Foxp3- T cells.
  
  
  RESULTS
  A numerical deficiency of circulating resting Tregs, activated Treg cells, and Tr1L was documented in patients with active IBD. Baseline levels of these Treg subsets predicted clinical responses to IFX. We documented an upregulation of all 3 subsets during IFX therapy. Moreover, after therapy, significant differences in Treg subsets were seen between responders and nonresponders to IFX. Restoration of Tregs correlated with the clinical and biological response to IFX therapy. Trough serum levels of IFX positively correlated with the proportion of activated Treg cells and Tr1L during therapy.
  
  
  CONCLUSIONS
  IFX therapy, when successful, results in upmodulation of the different types of Treg cells in the blood of patients with IBD. This effect might be relevant for understanding the mechanism of action of anti-TNF agents.
authors: *Clinical Immunology Unit, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; †Division of Gastroenterology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; ‡Laboratory of Pediatric Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; and §Department of Bioinformatics-Statistical Genetics, Université de Liège, Liège, Belgium.
authors: Zhe
authors: Z
authors: Li
authors: Séverine
authors: S
authors: Vermeire
authors: Dominique
authors: D
authors: Bullens
authors: Marc
authors: M
authors: Ferrante
authors: Kristel
authors: K
authors: Van Steen
authors: Maja
authors: M
authors: Noman
authors: Paul
authors: P
authors: Rutgeerts
authors: Jan L
authors: JL
authors: Ceuppens
authors: Gert
authors: G
authors: Van Assche
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D064368:Healthy Volunteers; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy*; D000069285:Infliximab / Q000627:therapeutic use*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D017493:Leukocyte Common Antigens