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Effects of FTY720 on rat lymphoid organs
Authors:Takai K  Takahara S  Isoyama N  Tsuchida M  Matsumura M  Kishi Y  Uchiyama K  Naito K
Affiliation:Department of Urology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan. takai@yamaguchi-u.ac.jp
Abstract:INTRODUCTION: In this study, we examined the in vivo effect of FTY720 on rat thymus and spleen. MATERIALS AND METHODS: Inbred male Lewis (RT-I(l)) rats, 5-weeks-old, received FTY720 (0.1, 1, or 10 mg/kg) by intramuscular injection into 1 of 4 limbs daily for 7 days. The rats were humanely killed at 1, 3, 5, or 7 days after starting administration of FTY720. The thymus and spleen were obtained for hematoxylin and eosin (HE) as well as immunoperoxidase staining using the antibodies OX8 (CD8), W3/25 (CD4), and OX6 (major histocompatibility complex class II). RESULTS: HE staining revealed marked atrophy in the cortical region of the thymus among rats administered FTY720 at the dose of 10 mg/kg. The atrophy extended to the whole cortex. On day 7 of administration of FTY 720 (10 mg/kg), the medulla of the thymus showed relative expansion due to cells accumulation. Also, the spleens of FTY720-treated rats revealed an obvious reduction in the T-cell-dependent areas around the central artery. In conclusion, the immunosuppressive effect of FTY720 may be due to an inhibitory effect on T-cell emigration from the thymus to the periphery.
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