Anti–TNF-α therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-β

• DOI: 10.1084/jem.20061531
• Publication Date: 2007-01-03T02:53:56Z
• Authors: Suchita Nadkarni; Claudia Mauri; Michael R. Ehrens...
• Keywords: Proinflammatory cytokine; Regulatory T cell

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