Abstract
Migration of hematopoietic precursor cells to the thymus is shown to depend upon a novel molecule called Vanin-1 expressed by perivascular thymic stromal cells. An anti-Vanin-1 antibody blocks the binding of pro-T cells to thymic sections in vitro, the in vivo accumulation of bone marrow cells around cortical thymic vessels, and long-term thymic regeneration. Thus, it interferes with the entry, and not the differentiation, of hematopoietic precursor cells. The Vanin-1 gene codes for a GPI-anchored 70 kDa protein that shows homology only with human biotinidase. Transfection of thymic stromal cells with the Vanin-1 cDNA enhances thymocyte adhesion in vitro. These data suggest that Vanin-1 regulates late adhesion steps of thymus homing under physiological, noninflammatory conditions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amidohydrolases
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal / chemistry
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Antibodies, Monoclonal / pharmacology
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Cell Adhesion Molecules / biosynthesis*
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / isolation & purification
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Cell Adhesion Molecules / physiology*
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Cell Differentiation / immunology
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Cell Line
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Cell Movement / immunology*
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GPI-Linked Proteins
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Glycosylphosphatidylinositols / metabolism*
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Hematopoietic Stem Cells / immunology*
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Immunosuppressive Agents / pharmacology
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Mice
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Mice, Inbred Strains
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Microcirculation / immunology
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Molecular Sequence Data
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Radiation Chimera / immunology
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Regeneration / immunology
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Staining and Labeling
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Stromal Cells / immunology
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T-Lymphocytes / immunology
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Thymus Gland / blood supply
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Thymus Gland / immunology*
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Thymus Gland / physiology
Substances
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Antibodies, Monoclonal
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Cell Adhesion Molecules
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GPI-Linked Proteins
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Glycosylphosphatidylinositols
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Immunosuppressive Agents
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Amidohydrolases
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pantetheinase