title: Involvement of inducible costimulator- and interleukin 10-positive regulatory T cells in the development of IgG4-related autoimmune pancreatitis.
abstract: OBJECTIVE
  Immunoglobulin G4 (IgG4)-related autoimmune pancreatitis (AIP) is a new clinical entity of pancreatic disorder. There are immunologic and histological abnormalities, including increased serum IgG4 levels and the infiltration of IgG4-positive plasmacytes. However, the role of IgG4 is unclear. Recently, regulatory T cells (Tregs) were reported to contribute to the development of various autoimmune diseases as well as in B-cell shifting to IgG4-producing plasmacytes. We studied Tregs in the pancreas and peripheral blood.
  
  
  METHODS
  We recruited 44 patients with IgG4-related AIP. For comparison, we recruited 37 patients with other pancreatic diseases and 27 healthy subjects as controls. We studied infiltrating cells in the pancreas by immunohistochemistry and analyzed inducible costimulator-positive Tregs and interleukin 10-positive Tregs in the peripheral blood by flow cytometry.
  
  
  RESULTS
  The ratio of Foxp3-positive cells to infiltrated mononuclear cells (Foxp3/Mono) in AIP patients was significantly higher than in patients with alcoholic chronic pancreatitis. In AIP, Foxp3/Mono and IgG4/Mono were positively correlated. Inducible costimulator-positive Tregs were significantly higher in AIP patients than in the patients with other pancreatic diseases and the healthy control group. Interleukin 10-positive Tregs were significantly higher in AIP patients than in the healthy control group.
  
  
  CONCLUSIONS
  Increased quantities of inducible costimulator-positive Tregs may influence IgG4 production in IgG4-related AIP.
authors.affiliation: Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Osaka, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Kusuda
authors.forename: Kazushige
authors.initials: K
authors.lastname: Uchida
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Masanori
authors.initials: M
authors.lastname: Koyabu
authors.forename: Sohei
authors.initials: S
authors.lastname: Satoi
authors.forename: Makoto
authors.initials: M
authors.lastname: Takaoka
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shikata
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Uemura
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007150:Immunohistochemistry; D060889:Inducible T-Cell Co-Stimulator Protein / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood*; D007564:Japan; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000276:immunology*; D010195:Pancreatitis / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C556692:ICOS protein, human; C508609:IL10 protein, human; D007074:Immunoglobulin G; D060889:Inducible T-Cell Co-Stimulator Protein; D016753:Interleukin-10