title: Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions.
abstract: The tissues of the central nervous system are effectively shielded from the blood circulation by specialized vessels that are impermeable not only to cells, but also to most macromolecules circulating in the blood. Despite this seemingly absolute seclusion, central nervous system tissues are subject to immune surveillance and are vulnerable to autoimmune attacks. Using intravital two-photon imaging in a Lewis rat model of experimental autoimmune encephalomyelitis, here we present in real-time the interactive processes between effector T cells and cerebral structures from their first arrival to manifest autoimmune disease. We observed that incoming effector T cells successively scanned three planes. The T cells got arrested to leptomeningeal vessels and immediately monitored the luminal surface, crawling preferentially against the blood flow. After diapedesis, the cells continued their scan on the abluminal vascular surface and the underlying leptomeningeal (pial) membrane. There, the T cells encountered phagocytes that effectively present antigens, foreign as well as myelin proteins. These contacts stimulated the effector T cells to produce pro-inflammatory mediators, and provided a trigger to tissue invasion and the formation of inflammatory infiltrations.
authors.affiliation: Max Planck Institute for Neurobiology, 82152 Martinsried, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Bartholomäus
authors.forename: Naoto
authors.initials: N
authors.lastname: Kawakami
authors.forename: Francesca
authors.initials: F
authors.lastname: Odoardi
authors.forename: Christian
authors.initials: C
authors.lastname: Schläger
authors.forename: Djordje
authors.initials: D
authors.lastname: Miljkovic
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Ellwart
authors.forename: Wolfgang E F
authors.initials: WE
authors.lastname: Klinkert
authors.forename: Cassandra
authors.initials: C
authors.lastname: Flügel-Koch
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Issekutz
authors.forename: Hartmut
authors.initials: H
authors.lastname: Wekerle
authors.forename: Alexander
authors.initials: A
authors.lastname: Flügel
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D002493:Central Nervous System Diseases / Q000276:immunology* / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D008578:Meninges / Q000098:blood supply* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010586:Phagocytes / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; D010047:Ovalbumin