title: Increase of regulatory T cells in ileal mucosa of untreated pediatric Crohn's disease patients.
abstract: BACKGROUND
  Inflammatory bowel disease (IBD) of pediatric and adult onset differs in several aspects although little knowledge exists about pathogenic disparity. Regulatory T cells (Tregs) characterized as CD4+CD25+Foxp3+ are modulators of gut homeostasis, but their role in human IBD remains unclear.
  
  
  OBJECTIVE
  To evaluate the mucosal distribution of Foxp3+ and CD25+ cells in untreated pediatric IBD patients at the time of diagnosis.
  
  
  METHODS
  Untreated pediatric (n = 14) and adult (n = 12) Crohn's disease (CD) patients were prospectively included together with age-matched symptomatic controls. Colonic and ileal mucosal biopsies collected at diagnosis were studied by immunohistochemistry for enumeration of T cells and for mucosal expression of Foxp3 and CD25. Multicolor immunofluorescence staining was performed in situ to phenotype Foxp3+ cells as Tregs and characterize the CD25+ cells.
  
  
  RESULTS
  The density of mucosal T cells displayed only small variations, while that of Foxp3+ cells and CD25+ cells was increased in CD patients. Multicolor immunofluorescence showed that most CD25+ cells were macrophages. Interestingly, in the ileum of pediatric CD patients the density of Foxp3+ cells was significantly higher than in adult CD patients. Co-expression of Foxp3 and CD25, as well as Foxp3 and CTLA-4, indicated that the Foxp3+ cells were Tregs.
  
  
  CONCLUSIONS
  Mucosal numbers of Foxp3(+) Tregs and activated (CD25+) macrophages are elevated in both pediatric and adult ileal CD. The greater increase of ileal Foxp3+ Tregs in pediatric CD than in adult CD might contribute to the relatively less frequent phenotype of isolated ileal enteritis in CD children.
authors.affiliation: Centre for Immune Regulation, Laboratory for Immunohistochemistry and Immunopathology, Department of Pathology, University of Oslo, Oslo, Norway. Dag.Henrik.Reikvam@rr-research.no
authors.forename: Dag Henrik
authors.initials: DH
authors.lastname: Reikvam
authors.forename: Gøri
authors.initials: G
authors.lastname: Perminow
authors.forename: Lars Gustav
authors.initials: LG
authors.lastname: Lyckander
authors.forename: Jon Michael
authors.initials: JM
authors.lastname: Gran
authors.forename: Per
authors.initials: P
authors.lastname: Brandtzaeg
authors.forename: Morten
authors.initials: M
authors.lastname: Vatn
authors.forename: Hege S
authors.initials: HS
authors.lastname: Carlsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015703:Antigens, CD / Q000378:metabolism; D060908:CTLA-4 Antigen; D002648:Child; D002675:Child, Preschool; D003092:Colitis / Q000378:metabolism / Q000473:pathology*; D003424:Crohn Disease / Q000473:pathology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007079:Ileitis / Q000378:metabolism / Q000473:pathology*; D007223:Infant; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit