Expression and function of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) in an in vitro model of the human blood--brain barrier.
The interaction of B7 molecules with their ligand provides important accessory signals for optimal T cell activation and proliferation. In this study the in vitro expression of B7-1 and B7-2 by human brain microvessel endothelial cells (HBMEC) was investigated by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry. In addition, the contribution of B7 molecules to T cell proliferation on cerebral endothelial cells was studied by coincubating purified CD4+ T cells with resting or cytokine activated HBMEC. Untreated cultures constitutively expressed B7-2 RNA and surface protein, but lacked B7-1 expression. Treatment with TNF-alpha and IFN-gamma upregulated B7-2 and induced de novo expression of B7-1. Monoclonal blocking antibodies to B7-1 or B7-2 and human CTLA-4Ig chimeric protein significantly reduced the ability of HBMEC to support alpha-CD3-induced proliferation of CD4+ T lymphocytes. Expression of B7 glycoproteins and the ability to provide secondary signals for T cell proliferation suggest a potential role of the human cerebral endothelium in T cell activation during the early stages of central nervous system inflammation.
Omari
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Department of Pathology and Laboratory Medicine, Neuropathology Research Laboratory, Vancouver General Hospital and the University of British Columbia, 855 West 12th Avenue, Vancouver, BC, V5Z 1M9, Canada.
Dorovini-Zis
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D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics* / Q000276:immunology*; D051940:B7-2 Antigen; D001812:Blood-Brain Barrier / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D017931:DNA Primers; D004727:Endothelium / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis
D015703:Antigens, CD; D000954:Antigens, Surface; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D017931:DNA Primers; D008562:Membrane Glycoproteins; D012333:RNA, Messenger