The Journal of Experimental Medicine
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Published online 9 August 2004 doi:10.1084/jem.20040643
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 4, 493-505
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CCR7 Signals Are Essential for Cortex–Medulla Migration of Developing Thymocytes

Tomoo Ueno1, Fumi Saito1, Daniel H.D. Gray2, Sachiyo Kuse1, Kunio Hieshima3, Hideki Nakano4, Terutaka Kakiuchi4, Martin Lipp5, Richard L. Boyd2, and Yousuke Takahama1

1 Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan
2 Department of Pathology and Immunology, Monash University Medical School, Victoria 3181, Australia
3 Department of Microbiology, Kinki University Medical School, Osaka 589-0014, Japan
4 Department of Immunology, Toho University School of Medicine, Tokyo 143-8594, Japan
5 Department of Molecular Tumorgenetics and Immunogenetics, Max-Delbrück Center for Molecular Medicine, Berlin 13092, Germany

Address correspondence to Yousuke Takahama, Div. of Experimental Immunology, Institute for Genome Research, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. Tel.: 81-88-633-9452; Fax: 81-88-633-9453; email: takahama{at}genome.tokushima-u.ac.jp

Upon TCR-mediated positive selection, developing thymocytes relocate within the thymus from the cortex to the medulla for further differentiation and selection. However, it is unknown how this cortex–medulla migration of thymocytes is controlled and how it controls T cell development. Here we show that in mice deficient for CCR7 or its ligands mature single-positive thymocytes are arrested in the cortex and do not accumulate in the medulla. These mutant mice are defective in forming the medullary region of the thymus. Thymic export of T cells in these mice is compromised during the neonatal period but not in adulthood. Thymocytes in these mice show no defects in maturation, survival, and negative selection to ubiquitous antigens. TCR engagement of immature cortical thymocytes elevates the cell surface expression of CCR7. These results indicate that CCR7 signals are essential for the migration of positively selected thymocytes from the cortex to the medulla. CCR7-dependent cortex–medulla migration of thymocytes plays a crucial role in medulla formation and neonatal T cell export but is not essential for maturation, survival, negative selection, and adult export of thymocytes.

Key Words: thymus • medulla • migration • CCR7 • positive and negative selection

Abbreviations used in this paper: DP, double positive; HPRT, hypoxanthine phosphoribosyltransferase; 4SP, CD4 single positive; 8SP, CD8 single positive; SP, single positive.


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