The role of CCL21 in recruitment of T-precursor cells to fetal thymi.
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.
Liu
Cunlan
C
Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan.
Ueno
Tomoo
T
Kuse
Sachiyo
S
Saito
Fumi
F
Nitta
Takeshi
T
Piali
Luca
L
Nakano
Hideki
H
Kakiuchi
Terutaka
T
Lipp
Martin
M
Hollander
Georg A
GA
Takahama
Yousuke
Y
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002478:Cells, Cultured; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D005312:Fetal Blood / Q000166:cytology; D005333:Fetus / Q000196:embryology / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008099:Liver / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology* / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D000906:Antibodies; C515479:Ccl21c protein, mouse; C491541:Ccl25 protein, mouse; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger