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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.

Original publication

DOI

10.1182/blood-2004-04-1369

Type

Journal article

Journal

Blood

Publication Date

01/01/2005

Volume

105

Pages

31 - 39

Keywords

Animals, Antibodies, Cells, Cultured, Chemokine CCL21, Chemokine CXCL12, Chemokines, CC, Chemokines, CXC, Chemotaxis, Leukocyte, Fetal Blood, Fetus, Histocompatibility Antigens Class II, Liver, Mice, Mice, Inbred C57BL, Mice, Knockout, RNA, Messenger, Stem Cells, T-Lymphocytes, Thymus Gland, Time Factors