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Therapy with antiTNF 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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