title: Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNFα treatment.
abstract: OBJECTIVE
  Inappropriate immune responses contribute to the continuous stimulation of the intestinal immune system in chronic inflammatory bowel disease (IBD). Among several pathogenic factors, a numerical deficiency of regulatory T (Treg) cells has been suggested to lead to an insufficient compensation of chronically activated T lymphocytes. This study was conducted to investigate whether increased apoptosis contributes to Treg cell deficiency in IBD and whether successful treatment with antitumour necrosis factor α (TNFα) is achieved by reducing of Treg cell apoptosis.
  
  
  METHODS
  Apoptosis of CD4(+)Foxp3(+) Treg cells in tissue sections of patients with active IBD was analysed by immunohistochemistry and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) staining. Apoptosis of peripheral blood CD4(+)CD25(+)Foxp3(+) Treg cells was investigated by flow cytometry and annexin-V staining. In addition, caspase activity and apoptosis were measured in sera of patients with IBD treated with anti-TNFα by a luminometric caspase enzyme assay.
  
  
  RESULTS
  It is demonstrated that patients with active IBD revealed increased apoptosis of local CD4(+)Foxp3(+) Treg cells in the inflamed mucosa compared with non-inflamed control colon tissue. Moreover, in peripheral blood a reduced frequency and increased apoptosis of Treg cells were found and accompanied by elevated caspase activity in the serum. During anti-TNFα treatment, Treg cell apoptosis declined in close correlation with elevated peripheral Treg cell numbers and a decrease of caspase activation and disease activity.
  
  
  CONCLUSIONS
  These data suggest that increased apoptosis of Treg cells plays a potentially important role in the pathogenesis of IBD and can be reversed by anti-TNFα treatment. Measurement of Treg cell apoptosis and serum caspase activity might therefore represent promising tools for monitoring disease activity and treatment response in patients with IBD.
authors: Department of Gastroenterology, Hepatology and Infectious Diseases, Ruprecht-Karls-University, Heidelberg, Germany.
authors: Claudia
authors: C
authors: Veltkamp
authors: Matthias
authors: M
authors: Anstaett
authors: Kristin
authors: K
authors: Wahl
authors: Sarah
authors: S
authors: Möller
authors: Saskia
authors: S
authors: Gangl
authors: Oliver
authors: O
authors: Bachmann
authors: Matthias
authors: M
authors: Hardtke-Wolenski
authors: Florian
authors: F
authors: Länger
authors: Wolfgang
authors: W
authors: Stremmel
authors: Michael P
authors: MP
authors: Manns
authors: Klaus
authors: K
authors: Schulze-Osthoff
authors: Heike
authors: H
authors: Bantel
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000276:immunology*; D001706:Biopsy; D002908:Chronic Disease; D003106:Colon / Q000276:immunology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D000069285:Infliximab; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab