PMID- 22057872 OWN - NLM STAT- MEDLINE DCOM- 20120430 LR - 20211021 IS - 1420-908X (Electronic) IS - 1023-3830 (Linking) VI - 61 IP - 1 DP - 2012 Jan TI - The effects of leflunomide on CD4(+)CD25 (+)Foxp3 (+) T regulatory cells in mice receiving allogeneic bone marrow transplantation. PG - 53-60 LID - 10.1007/s00011-011-0388-4 [doi] AB - OBJECTIVE AND DESIGN: Leflunomide (LEF) is effective not only in different animal models of autoimmune diseases and the therapy of patients with rheumatoid arthritisbut also in graft rejection. The effect of LEF on CD4(+)CD25(+)T regulatory cells (Treg) was determined in a mouse model of allogeneic bone marrow transplantation. MATERIAL OR SUBJECTS: BALB/c and C57BL/6 mice were used as donors and recipients, respectively. TREATMENT: C57BL/6 mice were given 2 Gy total-body irradiation, followed by an intravenous injection of 2 x 10(7) BALB/c bone marrow cells (BMCs). Mice were treated with LEF daily at a dose of 30 mg/kg/day for 2 weeks. RESULTS: In naive mice, LEF significantly decreased the percentage of CD4(+)CD25(+) Treg cells in spleens (P < 0.05), but not in lymph nodes, though LEF enhanced the percentages of CD4(+)CD25(+) Treg cells in CD4 single positive cells in the thymocytes and blood (P < 0.05). Furthermore, LEF significantly decreased the percentage of CD4(+)CD25(+) Treg cells in the spleens of mice that received allogeneic BMCs. CONCLUSIONS: LEF decreases peripheral CD4(+)CD25(+) Treg cells in un-immunizing and immunizing recipients, indicating that LEF might not be an ideal candidate for the treatment of autoimmune diseases or graft rejection with respect to induction of immune tolerance. FAU - Jin, Di AU - Jin D AD - Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. FAU - Duan, Kaizhong AU - Duan K FAU - Zhang, Lianjun AU - Zhang L FAU - Peng, Jianxia AU - Peng J FAU - Zhao, Yong AU - Zhao Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111105 PL - Switzerland TA - Inflamm Res JT - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JID - 9508160 RN - 0 (Antibodies, Monoclonal) RN - 0 (Forkhead Transcription Factors) RN - 0 (Foxp3 protein, mouse) RN - 0 (Interleukin-2 Receptor alpha Subunit) RN - 0 (Isoxazoles) RN - G162GK9U4W (Leflunomide) SB - IM MH - Animals MH - Antibodies, Monoclonal/chemistry MH - Autoimmune Diseases/metabolism MH - Bone Marrow Transplantation/*methods MH - CD4-Positive T-Lymphocytes/*cytology MH - Female MH - Forkhead Transcription Factors/*biosynthesis MH - Interleukin-2 Receptor alpha Subunit/*biosynthesis MH - Isoxazoles/*pharmacology MH - Leflunomide MH - Leukocytes, Mononuclear/cytology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - T-Lymphocytes, Regulatory/*cytology EDAT- 2011/11/08 06:00 MHDA- 2012/05/01 06:00 CRDT- 2011/11/08 06:00 PHST- 2011/02/08 00:00 [received] PHST- 2011/09/16 00:00 [accepted] PHST- 2011/08/23 00:00 [revised] PHST- 2011/11/08 06:00 [entrez] PHST- 2011/11/08 06:00 [pubmed] PHST- 2012/05/01 06:00 [medline] AID - 10.1007/s00011-011-0388-4 [doi] PST - ppublish SO - Inflamm Res. 2012 Jan;61(1):53-60. doi: 10.1007/s00011-011-0388-4. Epub 2011 Nov 5.