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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.
CHEMOKINES The role of CCL21 in recruitment of T-precursor cells to fetal thymiFrom 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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