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PMID:15358618
Citation |
Liu, C, Ueno, T, Kuse, S, Saito, F, Nitta, T, Piali, L, Nakano, H, Kakiuchi, T, Lipp, M, Hollander, GA and Takahama, Y (2005) The role of CCL21 in recruitment of T-precursor cells to fetal thymi. Blood 105:31-9 |
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Abstract |
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. CD4(-)CD8(-)CD25(-)CD44+ fetal thymocytes retained the activity to specifically re-enter the thymus. The attraction was predominantly due to I-A-expressing 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 CD4(-)CD8(-)CD25(-)CD44+ 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. |
Links |
PubMed Online version:10.1182/blood-2004-04-1369 |
Keywords |
Animals; Antibodies/immunology; Antibodies/pharmacology; Cells, Cultured; Chemokine CCL21; Chemokine CXCL12; Chemokines, CC/antagonists & inhibitors; Chemokines, CC/immunology; Chemokines, CC/metabolism; Chemokines, CXC/immunology; Chemokines, CXC/metabolism; Chemotaxis, Leukocyte; Fetal Blood/cytology; Fetus/embryology; Fetus/immunology; Fetus/metabolism; Histocompatibility Antigens Class II/immunology; Liver/cytology; Mice; Mice, Inbred C57BL; Mice, Knockout; RNA, Messenger/genetics; RNA, Messenger/metabolism; Stem Cells/cytology; Stem Cells/immunology; T-Lymphocytes/cytology; T-Lymphocytes/immunology; T-Lymphocytes/metabolism; Thymus Gland/cytology; Thymus Gland/embryology; Thymus Gland/immunology; Thymus Gland/metabolism; Time Factors |
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