Discrete changes in circulating regulatory T cells during infliximab treatment of Crohn's disease

Abstract

Deficiency of CD4+CD25+ regulatory T cells (Tregs) may be involved in Crohn's disease (CD) pathogenesis. In rheumatoid arthritis (RA), the anti-TNF-α antibody infliximab increases circulating Treg numbers. We aimed to evaluate circulating Tregs in CD before and after infliximab therapy. In 20 patients with active CD, blood samples were obtained before infusion of infliximab 5 mg/kg and 1, 7, and 42 days after therapy. Clinical, biochemical, and fecal markers of inflammation were obtained. Nine healthy volunteers served as controls. We applied a novel Treg marker, the absence of CD127 expression, to identify Tregs by whole-blood flow cytometry. Treg percentages were similar among CD patients [median 7.7%, interquartile range (IQR) 5.3–10.1%] and healthy volunteers (median 7.6% IQR 6.3–8.9%) with discrete changes (median 7.3%, IQR 4.5–10.1%) throughout the study period, irrespective of the significant clinical effect of infliximab. Unlike in RA, we found no arising population of CD62L − Tregs; however, we observed a rapid recruitment of lymphocytes and upregulation of the intestinal homing marker α4β7 integrin on CD4+T cells. In conclusion, our results do not support the hypothesis that the clinical effect of infliximab is mediated by a reinforcement of defective, circulating Tregs in CD.

Keywords::

• Crohn disease
• T-lymphocytes, regulatory
• biologic therapies

Acknowledgments

The authors wish to thank Rikke Andersen for technical assistance.

Declaration of interest: The study was financially supported by the Karen Elise Foundation, the Danish Colitis–Crohn Foundation, and the Toyota Foundation, Denmark. No author had personal financial interests, and no author received personal funding. The authors alone are responsible for the content and writing of the paper.