Leflunomide induces immunosuppression in collagen-induced arthritis rats by upregulating CD4+CD25+ regulatory T cells.
Author(s): Wang TY, Li J, Li CY, Jin Y, Lu XW, Wang XH, Zhou Q
Affiliation(s): School of Pharmacy, Anhui Medical University, Hefei 230032, China.
Publication date & source: 2010-01, Can J Physiol Pharmacol., 88(1):45-53.
Publication type: Comparative Study; Research Support, Non-U.S. Gov't
This study was to investigate the effect of leflunomide on the immunosuppressive CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) in collagen-induced arthritis (CIA) rats. CIA was induced by collagen type II in Wistar rats. Immunofluorescence flow cytometry and RT-PCR were used to determine the proportion of CD4+CD25+ Tregs and the expression of Foxp3 mRNA, respectively. Proliferation of T lymphocytes was assayed with MTT reagent, and the level of transforming growth factor beta1 (TGF-beta1) in the supernatant of concanavalin A (Con A)-induced T lymphocytes was determined by ELISA kit. Our investigations demonstrated that inhibition of arthritis by leflunomide was related to changes in CD4+CD25+ Tregs. In addition, A771726, which is the active metabolite of leflunomide, promoted the differentiation of spleen lymphocytes into CD4+CD25+ Tregs, increased antiinflammatory cytokine TGF-beta1 secretion, and adjusted the activity of Con A-induced lymphocytes in vitro.
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