The role of CCL21 in recruitment of T-precursor cells to fetal thymi

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 Tprecursor cells to the thymus remain unclear. By devising time-lapse visualization in culture, the present results show that alymphoid fetal thymus lobes attract Tprecursor 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. (Blood. 2005;105:31-39)

Effect of secondary lymphoid tissue chemokine suppression on experimental ulcerative colitis in mice

“…CCL21 has chemotactic effects on T, B, NK, and dendritic cells (DC) to peripheral lymphatic organs, and participates in several types of immune responses (Riedl et al, 2003;Stein et al, 2003;Liu et al, 2005;Legler et al, 2006;Ashour et al, 2007;Thanarajasingam et al, 2007;Gollmer et al, 2009;Fedele et al, 2011). Ashour et al (2007) reported that subcutaneous injection of CCL21 induced assembly of cytotoxic T lymphocytes (CTL) in draining lymph nodes, mainly the CD3 + , CD8 + , and CD62 -subpopulations.…”

Impaired Accumulation of Antigen-Specific CD8 Lymphocytes in Chemokine CCL25-Deficient Intestinal Epithelium and Lamina Propria

“…In the thymus, CCL25-CCR9 interactions appear to play an important role in the migration of early T cells into the cortex from the subcapsular zone after successful TCR␤ gene rearrangement (4 -7). CCR9 may also play an earlier role in thymic development, either by directly controlling thymic colonization (8 -10) or by participating in thymic precursor development within the bone marrow (BM) 3 (6,11,12).…”

Redefining epithelial progenitor potential in the developing thymus

“…This microenvironment provides key signals that support the recruitment of haemopoietic progenitors [3] as well as their subsequent development and selection. Thus, in the adult, the migration of T cell progenitors through thymic cortical regions to the subcapsular area is accompanied by their progression through the CD4 -CD8 -double-negative stages of development, involving differentiation, expansion and antigen receptor gene rearrangement [4,5].…”