Increase of regulatory T cells in ileal mucosa of untreated pediatric Crohn's disease patients

Scand J Gastroenterol. 2011 May;46(5):550-60. doi: 10.3109/00365521.2011.551887. Epub 2011 Feb 1.


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.

Material and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Antigens, CD / metabolism
  • CTLA-4 Antigen
  • Child
  • Child, Preschool
  • Colitis / metabolism
  • Colitis / pathology*
  • Crohn Disease / pathology*
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Ileitis / metabolism
  • Ileitis / pathology*
  • Infant
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology*
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Middle Aged
  • Prospective Studies
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology*
  • Young Adult


  • Antigens, CD
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit