Role of CCL21 in Recruitment of T Precursor Cells to Fetal Thymus

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. For personal use only. on October 3, 2017. by guest www.bloodjournal.org From