Stromal cells provide the matrix for migration of early lymphoid progenitors through the thymic cortex.
During steady state lymphopoiesis in the postnatal thymus, migration of precursors outward from the deep cortex toward the capsule is required for normal differentiation. Such migration requires, at a minimum, expression of adhesive receptors on the migrating lymphoid cells, as well as a stable matrix of their ligands persisting throughout the region of migration. In this study, we address the nature of this adhesive matrix. Although some precursor stages bound efficiently to extracellular matrix ligands, a specific requirement for the cell surface ligand VCAM-1 was also found. In situ analysis revealed that early precursors are found in intimate contact with a matrix formed by stromal cells in the cortex, a proportion of which expresses VCAM-1. In vivo administration of an anti-VCAM-1 Ab resulted in decreased thymic size and altered distribution of early precursors within the cortex. These results indicate that precursors migrating outward through the cortex may use a cellular, rather than extracellular, matrix for adhesion, and suggest that the VCAM-1(+) subset of cortical stroma may play a crucial role in supporting the migration of early precursors in the steady state thymus.
Prockop
Susan E
SE
Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Palencia
Sharina
S
Ryan
Christina M
CM
Gordon
Kristie
K
Gray
Daniel
D
Petrie
Howard T
HT
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D016326:Extracellular Matrix Proteins / Q000276:immunology / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D007272:Injections, Intralymphatic; D016023:Integrins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000033:anatomy & histology / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D000911:Antibodies, Monoclonal; D016326:Extracellular Matrix Proteins; D016023:Integrins; D019010:Vascular Cell Adhesion Molecule-1