Ueha Satoshi, Yoneyama Hiroyuki, Hontsu Shigeto, Kurachi Makoto, Kitabatake Masahiro, Abe Jun, Yoshie Osamu, Shibayama Shiro, Sugiyama Tetsuya, Matsushima Kouji
Department of Molecular Preventive Medicine and SORST, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo, Japan.
J Leukoc Biol. 2007 Nov;82(5):1230-8. doi: 10.1189/jlb.0906574. Epub 2007 Aug 14.
Thymus-derived forkhead box p3(+) naturally occurring regulatory T cells (nTreg) are thought to circulate throughout the body to maintain peripheral immunological self-tolerance through interactions with dendritic cells (DCs), resulting in regulation of conventional T cells. However, the chemokine receptors, which are putatively involved in the in vivo migration of nTreg, have not been fully established. Here, we demonstrated that lymph node nTreg preferentially migrated to the paracortical area of lymph nodes after adoptive transfer, where they were observed to make contact frequently with CD8alpha(+) DCs and CD8alpha(-) CD11b(-) DCs. This migration of nTreg to the paracortical areas was impaired severely when cells were prepared from CCR7-deficient mice. However, to some extent, CCR7-independent migration of nTreg in such CCR7-deficient mice was also observed, but this occurred mainly in the medullary high endothelial venules. Taken together, these data provide the evidence that CCR7 mediates nTreg migration to the paracortical areas of lymph nodes under steady-state conditions; however, CCR7-independent migration also takes place in the medulla.
胸腺来源的叉头框蛋白3(+)自然调节性T细胞(nTreg)被认为在全身循环,通过与树突状细胞(DC)相互作用维持外周免疫自身耐受性,从而调节常规T细胞。然而,推测参与nTreg体内迁移的趋化因子受体尚未完全明确。在此,我们证明,过继转移后,淋巴结nTreg优先迁移至淋巴结的副皮质区,在该区域观察到它们频繁与CD8α(+)DC和CD8α(-)CD11b(-)DC接触。当从CCR7缺陷小鼠制备细胞时,nTreg向副皮质区的这种迁移严重受损。然而,在这种CCR7缺陷小鼠中,也在一定程度上观察到nTreg的不依赖CCR7的迁移,但这种迁移主要发生在髓质高内皮微静脉。综上所述,这些数据证明CCR7在稳态条件下介导nTreg向淋巴结副皮质区的迁移;然而,不依赖CCR7的迁移也发生在髓质。
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