Published online before print August 14, 2007

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0906574

Received for publication September 18, 2006.
Revised July 2, 2007.
Accepted for publication July 4, 2007.

Article

CCR7 mediates the migration of Foxp3⁺ regulatory T cells to the paracortical areas of peripheral lymph nodes through high endothelial venules

Satoshi Ueha ^*, Hiroyuki Yoneyama ^*, Shigeto Hontsu , Makoto Kurachi ^*, Masahiro Kitabatake ^*, Jun Abe ^*, Osamu Yoshie , Shiro Shibayama , Tetsuya Sugiyama , and Kouji Matsushima ^*@

*Department of Molecular Preventive Medicine & SORST, Graduate School of Medicine, The University of Tokyo, Japan; Second Department of Internal Medicine, Nara Medical University, Japan; Department of Microbiology, Kinki University School of Medicine, Japan; and Exploratory Research Laboratories, Ono Pharmaceutical Co., Ltd., Japan

^@ To whom correspondence should be addressed. E-mail: koujim{at}m.u-tokyo.ac.jp.

Abstract

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 CD8⁺ DCs and CD8^– 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.

Key Words: chemokine • cell migration • medulla • migration • tolerance

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