rApoptosis 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 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 a (TNFa) 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- TNFa 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-TNFa 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-TNFa 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. [ABSTRACT FROM AUTHOR]