Factors regulating stem cell recruitment to the fetal thymus.
Colonization of the thymic rudiment during development is initiated before vascularization so that hemopoietic precursors must leave the pharyngeal vessels and migrate through the perithymic mesenchyme to reach the thymus, suggesting that they may be responding to a gradient of chemoattractant factors. We report that diffusible chemoattractants are produced by MHC class II+ epithelial cells of the fetal thymus, and that the response of precursors to these factors is mediated via a G protein-coupled receptor, consistent with factors being members of the chemokine family. Indeed, a number of chemokine receptors are expressed by thymic precursors, and several chemokines are also expressed by thymic epithelial cells. However, these chemokines are also expressed in a tissue that is unable to attract precursors, although the thymus expressed chemokine, TECK, is expressed at higher levels in thymic epithelial cells and we show that it has chemotactic activity for isolated thymic precursors. Neutralizing Ab to TECK, however, did not prevent thymus recolonization by T cell precursors, suggesting that other novel chemokines might be involved in this process. In addition, we provide evidence for the involvement of matrix metalloproteinases in chemoattractant-mediated T cell precursor recruitment to the thymus during embryogenesis.
Wilkinson
B
B
Department of Anatomy, The Medical School, University of Birmingham, United Kingdom. Beverley@scripps.edu
Owen
J J
JJ
Jenkinson
E J
EJ
D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D019742:Chemokines, CC / Q000502:physiology; D002630:Chemotactic Factors / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005333:Fetus; D005374:Filtration; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009924:Organ Culture Techniques; D011956:Receptors, Cell Surface / Q000502:physiology; D019707:Receptors, Chemokine / Q000096:biosynthesis; D012995:Solubility; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology* / Q000276:immunology / Q000378:metabolism
C491541:Ccl25 protein, mouse; D019742:Chemokines, CC; D002630:Chemotactic Factors; D000949:Histocompatibility Antigens Class II; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D008666:Metalloendopeptidases; D019204:GTP-Binding Proteins