Abstract
The chemokine interferon (IFN)-gamma-inducible protein of 10 kDa (IP-10; CXCL10) has been implicated in recruitment of T cells into rejecting allografts yet appears ineffective at stimulating human peripheral blood CD4 T cells to transmigrate across tumor necrosis factor (TNF)-treated human endothelial cell (EC) monolayers in vitro. The same cells rapidly (within 15 min) transmigrate across TNF-treated EC monolayers overlaid with stromal cell-derived factor-1 alpha (SDF-1 alpha) and subjected to shear stress. The effector memory subset within the CD4 T cell population, defined as CD45RO, CD62L and CCR7, which constitutes less than 10% of total CD4 T cells, does respond to IP-10 but requires enrichment to be observed in this model. Central memory T cells do not respond to IP-10. Transendothelial migration of effector memory CD4 T cells requires TNF-pretreatment of the EC monolayer and application of venular shear force during the assay. TNF treatment of ECs may be effectively replaced by transduction of vascular cell adhesion molecule-1 or intercellular adhesion molecule-1 but not E-selectin.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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Cell Adhesion
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / physiology*
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Cell Communication / immunology*
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Cell Movement / genetics
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Cells, Cultured
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Chemokine CXCL10
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Chemokine CXCL12
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Chemokines, CXC / pharmacology*
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Endothelial Cells / drug effects
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Endothelial Cells / immunology*
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Endothelium, Vascular / cytology
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Endothelium, Vascular / immunology*
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Graft Rejection / genetics
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Graft Rejection / immunology*
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Humans
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / physiology
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L-Selectin / analysis
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Leukocyte Common Antigens / analysis
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Receptors, CCR7
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Receptors, Chemokine / analysis
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Stress, Mechanical
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T-Lymphocyte Subsets / drug effects*
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T-Lymphocyte Subsets / immunology
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Transduction, Genetic
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Tumor Necrosis Factors / pharmacology
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Vascular Cell Adhesion Molecule-1 / genetics
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Vascular Cell Adhesion Molecule-1 / physiology
Substances
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CCR7 protein, human
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CXCL12 protein, human
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Cell Adhesion Molecules
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Chemokine CXCL10
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Chemokine CXCL12
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Chemokines, CXC
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Receptors, CCR7
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Receptors, Chemokine
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Tumor Necrosis Factors
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Vascular Cell Adhesion Molecule-1
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Intercellular Adhesion Molecule-1
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L-Selectin
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Leukocyte Common Antigens