The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20061531
The Journal of Experimental Medicine, Vol. 204, No. 1, 33-39
The Rockefeller University Press, 0022-1007 $30.00
© Nadkarni et al.
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BRIEF DEFINITIVE REPORT

 Anti–TNF-{alpha} therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-ß

Suchita Nadkarni, Claudia Mauri, and Michael R. Ehrenstein

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

CORRESPONDENCE Claudia Mauri: c.mauri{at}ucl.ac.uk

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– 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)-ß 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-ß. 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.

C. Mauri and M.R. Ehrenstein contributed equally to this work.


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