title: Regulation of cellular and molecular trafficking across human brain endothelial cells by Th1- and Th2-polarized lymphocytes.
abstract: We used adult human brain-derived endothelial cells (HBECs) to model migration of peripheral blood lymphocytes across the blood brain barrier (BBB) as occurs in MS. We demonstrate that enhanced expression of adhesion molecule ICAM-1 and production of chemokines CXCL10/IP-10, CCL2/MCP-1, and CXCL8/IL-8 by HBECs induced by supernatants derived from allogeneic or myelin basic protein-reactive Th1 cells is only partially reversed with anti-IFNgamma antibody. This effect is not reproduced with IFNgamma or TNFalpha alone, implicating the interaction of multiple factors in the overall functional response. Supernatants from Th2 cells neither suppressed nor amplified Th1-induced effects. Although both Th1 and Th2 supernatants modulated the expression and localization of tight junction molecules zonula occludens (ZO)-1 and ZO-2, neither supernatant altered the permeability of HBEC monolayers to albumin or increased subsequent T cell migration rates. Prior migration of Th1 or Th2 cells across HBECs did enhance subsequent passage of cells and soluble molecules. Our results suggest that initial infiltration of either Th1 or Th2 polarized lymphocytes across the BBB contributes to the continuation of an inflammatory response in the central nervous system.
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Biernacki
authors.forename: Alexandre
authors.initials: A
authors.lastname: Prat
authors.forename: Manon
authors.initials: M
authors.lastname: Blain
authors.forename: Jack P
authors.initials: JP
authors.lastname: Antel
mesh_terms: D000328:Adult; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D010750:Phosphoproteins / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein
chemical_list: D018925:Chemokines; D017077:Culture Media, Conditioned; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; C569046:TJP2 protein, human; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma