title: Induction of regulatory T cells by infliximab in Behcet's disease.
abstract: OBJECTIVE
  To determine whether infliximab induces the development of Foxp3+ T regulatory (Treg) cells in patients with Behçet's disease.
  
  
  METHODS
  The subjects were patients with refractory uveitis caused by Behçet's disease, Vogt-Koyanagi-Harada disease, or ocular toxoplasmosis and healthy volunteers. Purified CD4+ T cells were obtained from patients with uveitis who were treated with colchicine, cyclosporine, or infliximab. Flow cytometry was used to analyze the expression of Foxp3 on CD4+ T cells.
  
  
  RESULTS
  Foxp3 was expressed in a small percentage of CD4+ T cells (<5%) from healthy subjects and from patients with active uveitis caused by Behçet's disease, Vogt-Koyanagi-Harada disease, or ocular toxoplasmosis. The percentage of Foxp3+ cells among CD4+ T cells was significantly decreased in patients with active uveitis compared with patients with inactive uveitis in the remission stage. Foxp3 was expressed at a similar level in CD4+ T cells from healthy donors, colchicine-treated patients, and cyclosporine-treated patients, whereas infliximab-treated patients expressed much higher percentages of Foxp3+ cells. Patients who had a high population of Foxp3+ cells during infliximab treatment did not experience any subsequent episodes of acute uveitis. On the other hand, patients with a low population of Foxp3+ cells did experience ocular inflammatory episodes. T cells exposed to infliximab in vitro greatly expressed Foxp3 and produced TGFβ, and the Treg cells significantly suppressed the activation of bystander T cells in vitro.
  
  
  CONCLUSIONS
  Anti-TNF-α therapy may be useful for patients with ocular complications of Behçet's disease who have a decreased percentage of peripheral Treg cells.
authors.affiliation: Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine and Dental Sciences, Tokyo, Japan. sunaoph@tmd.ac.jp
authors.forename: Sunao
authors.initials: S
authors.lastname: Sugita
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Shintaro
authors.initials: S
authors.lastname: Horie
authors.forename: Manabu
authors.initials: M
authors.lastname: Mochizuki
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001528:Behcet Syndrome / Q000188:drug therapy* / Q000276:immunology; D003078:Colchicine / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D000069285:Infliximab; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014126:Toxoplasmosis, Ocular / Q000188:drug therapy / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014605:Uveitis / Q000188:drug therapy / Q000276:immunology; D014607:Uveomeningoencephalitic Syndrome / Q000188:drug therapy / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine; D000069285:Infliximab; D003078:Colchicine