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Blood, 1 January 2005, Vol. 105, No. 1, pp. 31-39.
Prepublished online as a Blood First Edition Paper on September 9, 2004; DOI 10.1182/blood-2004-04-1369.
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CHEMOKINES
The role of CCL21 in recruitment of T-precursor cells to fetal thymi
Cunlan Liu,
Tomoo Ueno,
Sachiyo Kuse,
Fumi Saito,
Takeshi Nitta,
Luca Piali,
Hideki Nakano,
Terutaka Kakiuchi,
Martin Lipp,
Georg A. Hollander, and
Yousuke Takahama
From the Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan; Pediatric Immunology, Department of Research, University of Basel, Basel, Switzerland; Department of Immunology, Toho University School of Medicine, Tokyo, Japan; and Department of Tumor Genetics and Immunogenetics, Max-Delbruck Center for Molecular Medicine, Berlin, Germany.
During embryonic development, T-lymphoid precursor cells colonize the thymus. Chemoattraction by the fetal thymus is thought to mediate T-precursor cell colonization. However, the molecules that attract T-precursor cells to the thymus remain unclear. By devising time-lapse visualization in culture, the present results show that alymphoid fetal thymus lobes attract T-precursor cells from fetal liver or fetal blood. CD4CD8CD25CD44+ fetal thymocytes retained the activity to specifically re-enter the thymus. The attraction was predominantly due to I-Aexpressing thymic epithelial cells and was mediated by pertussis toxin-sensitive G-protein signals. Among the chemokines produced by the fetal thymus, CCL21, CCL25, and CXCL12 could attract CD4CD8CD25CD44+ fetal thymocytes. However, fetal thymus colonization was markedly diminished by neutralizing antibodies specific for CCL21 and CCL25, but not affected by anti-CXCL12 antibody. Fetal thymus colonization was partially defective in CCL21-deficient plt/plt mice and was further diminished by anti-CCL25 antibody. These results indicate that CCL21 is involved in the recruitment of T-cell precursors to the fetal thymus and suggest that the combination of CCL21 and CCL25 plays a major role in fetal thymus colonization.

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