Abstract
Human effector memory (EM) CD4(+) T cells can rapidly transmigrate across an endothelial cell (EC) monolayer in response either to chemokine or to TCR-activating signals displayed by human dermal microvascular EC under conditions of venular shear stress. We previously reported that the TCR-stimulated transendothelial migration (TEM) depends on fractalkine (CX3CL1), PECAM-1 (CD31), and ICAM-1 (CD54) expression by the EC, whereas chemokine-stimulated TEM does not. In this study, we further analyze these responses using blocking mAb and small interfering RNA knockdown to show that TCR-stimulated TEM depends on CD99 on EC as well as on PECAM-1 and depends on nectin-2 (CD112) and poliovirus receptor (CD155) as well as EC ICAM-1. ICAM-1 is engaged by EM CD4(+) T cell LFA-1 (CD11a/CD18) but not Mac-1 (CD11b/CD18); nectin-2 and poliovirus receptor are engaged by both DNAX accessory molecule-1 (CD226) and Tactile (CD96). EC junctional adhesion molecule-1 (JAM-1), an alternative ligand for LFA-1, contributes exclusively to chemokine-stimulated TEM and ICAM-2 appears to be uninvolved in either pathway. These data further define and further highlight the differences in the two pathways of EM CD4(+) T cell recruitment into sites of peripheral inflammation.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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12E7 Antigen
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Antibodies, Blocking / pharmacology
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Antigens, CD / biosynthesis
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Antigens, CD / metabolism
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Antigens, CD / physiology
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Cell Adhesion Molecules / antagonists & inhibitors
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Cell Adhesion Molecules / biosynthesis
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Cell Adhesion Molecules / immunology
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Cell Adhesion Molecules / metabolism
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Cell Adhesion Molecules / physiology*
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Cell Communication / immunology*
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Cell Movement / immunology*
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Cells, Cultured
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Chemokines / metabolism
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Chemokines / physiology
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Endothelium, Vascular / cytology
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Endothelium, Vascular / immunology*
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Endothelium, Vascular / metabolism*
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Humans
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Immunologic Memory*
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Junctional Adhesion Molecules
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Lymphocyte Function-Associated Antigen-1 / biosynthesis
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Lymphocyte Function-Associated Antigen-1 / metabolism
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Lymphocyte Function-Associated Antigen-1 / physiology
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Nectins
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Receptors, Antigen, T-Cell / antagonists & inhibitors
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Receptors, Antigen, T-Cell / physiology*
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Receptors, Virus / physiology
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Signal Transduction / immunology
Substances
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12E7 Antigen
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Antibodies, Blocking
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Antigens, CD
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CD99 protein, human
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Cell Adhesion Molecules
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Chemokines
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ICAM2 protein, human
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Junctional Adhesion Molecules
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Lymphocyte Function-Associated Antigen-1
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Nectins
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Receptors, Antigen, T-Cell
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Receptors, Virus
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poliovirus receptor