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J Exp Med. 2007 Jan 22;204(1):33-9. Epub 2007 Jan 2.

Anti-TNF-alpha therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-beta.

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  • 1Centre For Rheumatology, Department of Medicine, Windeyer Institute, University College London, London W1T 4JF, England, UK.

Erratum in

  • J Exp Med. 2007 Jan 22;204(1):205.

Abstract

The induction of regulatory T (T reg) cells holds considerable potential as a treatment for autoimmune diseases. We have previously shown that CD4+CD25hi T reg cells isolated from patients with active rheumatoid arthritis (RA) have a defect in their ability to suppress proinflammatory cytokine production by CD4+CD25- [corrected] T cells. This defect, however, was overcome after anti-tumor necrosis factor (TNF)-alpha antibody (infliximab) therapy. Here, we demonstrate that infliximab therapy gives rise to a CD4+CD25hiFoxP3+ T reg cell population, which mediates suppression via transforming growth factor (TGF)-beta and interleukin 10, and lacks CD62L expression, thereby distinguishing this T reg cell subset from natural T reg cells present in healthy individuals and patients with active RA. In vitro, infliximab induced the differentiation of CD62L- T reg cells from CD4+CD25- T cells isolated from active RA patients, a process dependent on TGF-beta. In spite of the potent suppressor capacity displayed by this CD62L- T reg cell population, the natural CD62L+ T reg cells remained defective in infliximab-treated patients. These results suggest that anti-TNF-alpha therapy in RA patients generates a newly differentiated population of T reg cells, which compensates for the defective natural T reg cells. Therefore, manipulation of a proinflammatory environment could represent a therapeutic strategy for the induction of T reg cells and the restoration of tolerance.

PMID:
17200409
[PubMed - indexed for MEDLINE]
PMCID:
PMC2118431
Free PMC Article
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