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Therapy with anti-TNFα antibody enhances number and function of Foxp3+ regulatory T cells in inflammatory bowel diseases

Boschetti, Gilles1,2; Nancey, Stéphane1,2; Sardi, Fatima1; Roblin, Xavier3; Flourié, Bernard1,2; Kaiserlian, Dominique1

doi: 10.1002/ibd.21308
Original Clinical Articles

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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

Email: dominique.kaiserlian@inserm.fr

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.

© Crohn's & Colitis Foundation of America, Inc.
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