Fujii Toshimitsu, Tomita Takayuki, Kanai Takanori, Nemoto Yasuhiro, Totsuka Teruji, Sakamoto Naoya, Nakamura Tetsuya, Tsuchiya Kiichiro, Okamoto Ryuichi, Watanabe Mamoru
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Eur J Immunol. 2008 Dec;38(12):3290-303. doi: 10.1002/eji.200838359.
2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol hydrochloride (FTY720) suppresses T-cell egress from LN, thereby preventing pathogenic T cells from migrating toward disease sites. However, little is known about whether FTY720 could control the trafficking of T cells without the presence of lymphoid tissues. Here we demonstrate that FTY720 treatment suppresses the recirculation of CD4(+) T cells in splenectomized (SPX) lymphotoxin-alpha(-/-) (LT-alpha(-/-)) mice that lack LN and spleen, as shown by peripheral blood (PB) lymphopenia in FTY720-treated SPX LT-alpha(-/-) mice. In a short-term transfer experiment, the cell number of transferred Ly5.1(+)CD4(+) T cells recovered from host FTY720-treated SPX LT-alpha(-/-) mice (Ly5.2(+)) was markedly decreased in PB, but conversely increased in BM. Notably, FTY720 treatment prevented the development of colitis that is otherwise induced in untreated SPX LT-alpha(-/-) x RAG-2(-/-) mice upon transfer of colitic lamina propria CD4(+) T cells. In such mice, the number of CD4(+) T cells in PB or lamina propria of FTY720-treated SPX LT-alpha(-/-) x RAG-2(-/-) recipients was significantly reduced, but that in the BM was significantly increased as compared with untreated control mice. Altogether, the present results indicate that FTY720 treatment may offer an additional role to direct trafficking of CD4(+) T cells in BM, resulting in the prevention of colitis.
盐酸2-氨基-2-(2-[4-辛基苯基]乙基)-1,3-丙二醇(FTY720)可抑制T细胞从淋巴结流出，从而阻止致病性T细胞向疾病部位迁移。然而，关于FTY720在没有淋巴组织的情况下是否能够控制T细胞的迁移，人们知之甚少。在此我们证明，FTY720处理可抑制脾切除(SPX)的淋巴毒素α基因敲除(LT-α-/-)小鼠(缺乏淋巴结和脾脏)中CD4(+)T细胞的再循环，这表现为经FTY720处理的SPX LT-α-/-小鼠外周血(PB)淋巴细胞减少。在一项短期转移实验中，从经FTY720处理的宿主SPX LT-α-/-小鼠(Ly5.2(+))中回收的转移Ly5.1(+)CD4(+)T细胞的细胞数量在PB中显著减少，但在骨髓中反而增加。值得注意的是，FTY720处理可预防结肠炎的发生，否则在将结肠炎固有层CD4(+)T细胞转移至未处理的SPX LT-α-/-×RAG-2-/-小鼠时会诱发结肠炎。在这类小鼠中，与未处理的对照小鼠相比，经FTY720处理的SPX LT-α-/-×RAG-2-/-受体的PB或固有层中CD4(+)T细胞数量显著减少，但骨髓中的数量显著增加。总之，目前的结果表明，FTY720处理可能在引导CD4(+)T细胞向骨髓迁移方面发挥额外作用，从而预防结肠炎。
