Leflunomide induces immunosuppression in collagen-induced arthritis rats by upregulating CD4+CD25+ regulatory T cells.
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.
Wang
Ting-Yu
TY
School of Pharmacy, Anhui Medical University, Hefei 230032, China.
Li
Jun
J
Li
Chang-Yu
CY
Jin
Yong
Y
Lü
Xiong-Wen
XW
Wang
Xiao-Hua
XH
Zhou
Qian
Q
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000096:biosynthesis; D002417:Cattle; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077339:Leflunomide; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D015704:CD4 Antigens; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D007555:Isoxazoles; D000077339:Leflunomide