title: Identification of endothelial cell junctional proteins and lymphocyte receptors involved in transendothelial migration of human effector memory CD4+ T cells.
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.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Manes
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Pober
mesh_terms: D000071443:12E7 Antigen; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D062726:Junctional Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D000075983:Nectins; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000071443:12E7 Antigen; D019138:Antibodies, Blocking; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D018925:Chemokines; C065289:ICAM2 protein, human; D062726:Junctional Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D000075983:Nectins; D011948:Receptors, Antigen, T-Cell; D011991:Receptors, Virus; C066100:poliovirus receptor