Inflammatory bowel diseases (IBDs) are associated with up-regulation of TNFα, hyperactivation of proinflammatory effector T cells (Teffs) and inefficient control by regulatory CD4+CD25+Foxp3+ T cells (Tregs). The aim of this prospective study was to investigate the short-term impact of treatment of IBD patients with anti-TNFα antibodies (infliximab or adalimumab) on the frequency, phenotype, and suppressive function of Tregs.
Active IBD patients including 16 with Crohn's disease and 9 with ulcerative colitis were treated with anti-TNFα mAb. PBMCs were harvested immediately before and 2 weeks after the first injection. The frequency and phenotype of circulating CD4+CD25+Foxp3+ Tregs were analyzed by flow cytometry, and their suppressive function was assessed by the ability of purified CD4+CD25+CD127− Tregs to inhibit the proliferation of allogenic CD4+CD25− Teffs.
CD4+CD25+Foxp3+ Treg frequency was significantly lower in active IBD patients than in controls (2.8% ± 0.4% vs. 4.6% ± 0.6%, respectively; P = 0.01). On day 14 following the first anti-TNFα infusion, the frequency of circulating Tregs was significantly enhanced in IBD patients (4.0% ± 0.5% vs. 2.8% ± 0.4%, before treatment; P = 0.001), with a 2- to 3-fold increase in the intensity of Foxp3 expression. In addition, infliximab treatment enhanced the suppressive function of circulating Tregs, as shown by inhibition of Teff proliferation at a 1:8 Treg/Teff ratio (28% ± 5% vs. 66% ± 10%, after treatment; P = 0.04).
These data demonstrate that anti-TNFα treatment of active IBD rapidly enhances the frequency of functional Foxp3+ Tregs in blood and potentiates their suppressive function. This indicates that Treg potentiation may represent an unanticipated outcome of anti-TNFα biotherapy in IBD. (Inflamm Bowel Dis 2011;)
1INSERM U 851 “Immunité et Vaccination,” CERVI, IFR 128 Biosciences Lyon Gerland, Lyon, France
2Hospices Civils de Lyon, Service de Gastroentérologie, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
3Service de Gastroentérologie, CHU Hôpital Nord, Saint-Etienne, France
Reprints: INSERM-U851, 21 Av. Tony Garnier, 69365 LYON CX 07, FRANCE
Received 5 February 2010; Accepted 5 March 2010
Grant sponsor: Institut National de la Santé et de la Recherche Médicale and by the Association François Aupetit.
Gilles Boschetti and Stéphane Nancey are co–first authors.