The effects of leflunomide on CD4(+)CD25 (+)Foxp3 (+) T regulatory cells in mice receiving allogeneic bone marrow transplantation.

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 × 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 naïve 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.