%0 Journal Article %A Claudia Veltkamp %A Matthias Anstaett %A Kristin Wahl %A Sarah Möller %A Saskia Gangl %A Oliver Bachmann %A Matthias Hardtke-Wolenski %A Florian Länger %A Wolfgang Stremmel %A Michael P Manns %A Klaus Schulze-Osthoff %A Heike Bantel %T Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNFα treatment %D 2011 %R 10.1136/gut.2010.217117 %J Gut %P 1345-1353 %V 60 %N 10 %X Background and aims 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. %U https://gut.bmj.com/content/gutjnl/60/10/1345.full.pdf