Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNFα treatment

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...

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Main Authors: Veltkamp, Claudia (Author) , Anstaett, Matthias (Author) , Wahl, Kristin (Author) , Möller, Sarah (Author) , Gangl, Saskia (Author) , Bachmann, Oliver (Author) , Hardtke-Wolenski, Matthias (Author) , Länger, Florian (Author) , Stremmel, Wolfgang (Author) , Manns, Michael P. (Author) , Schulze-Osthoff, Klaus (Author) , Bantel, Heike (Author)
Format: Article (Journal)
Language:English
Published: 1 April 2011
In: Gut
Year: 2011, Volume: 60, Issue: 10, Pages: 1345-1353
ISSN:1468-3288
DOI:10.1136/gut.2010.217117
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1136/gut.2010.217117
Verlag, lizenzpflichtig, Volltext: https://gut.bmj.com/content/60/10/1345
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Author Notes:Claudia Veltkamp, Matthias Anstaett, Kristin Wahl, Sarah Möller, Saskia Gangl, Oliver Bachmann, Matthias Hardtke-Wolenski, Florian Länger, Wolfgang Stremmel, Michael P. Manns, Klaus Schulze-Osthoff, Heike Bantel

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520 |a 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. 
650 4 |a anti-TNFα 
650 4 |a Apoptosis 
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650 4 |a inflammatory bowel disease 
650 4 |a Treg cells 
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