title: T-Lymphocytes Traffic into the Brain across the Blood-CSF Barrier: Evidence Using a Reconstituted Choroid Plexus Epithelium.
abstract: An emerging concept of normal brain immune surveillance proposes that recently and moderately activated central memory T lymphocytes enter the central nervous system (CNS) directly into the cerebrospinal fluid (CSF) via the choroid plexus. Within the CSF space, T cells inspect the CNS environment for cognate antigens. This gate of entry into the CNS could also prevail at the initial stage of neuroinflammatory processes. To actually demonstrate T cell migration across the choroidal epithelium forming the blood-CSF barrier, an in vitro model of the rat blood-CSF barrier was established in an "inverse" configuration that enables cell transmigration studies in the basolateral to apical, i.e. blood/stroma to CSF direction. Structural barrier features were evaluated by immunocytochemical analysis of tight junction proteins, functional barrier properties were assessed by measuring the monolayer permeability to sucrose and the active efflux transport of organic anions. The migratory behaviour of activated T cells across the choroidal epithelium was analysed in the presence and absence of chemokines. The migration pathway was examined by confocal microscopy. The inverse rat BCSFB model reproduces the continuous distribution of tight junction proteins at cell margins, the restricted paracellular permeability, and polarized active transport mechanisms, which all contribute to the barrier phenotype in vivo. Using this model, we present experimental evidence of T cell migration across the choroidal epithelium. Cell migration appears to occur via a paracellular route without disrupting the restrictive barrier properties of the epithelial interface. Apical chemokine addition strongly stimulates T cell migration across the choroidal epithelium. The present data provide evidence for the controlled migration of T cells across the blood-CSF barrier into brain. They further indicate that this recruitment route is sensitive to CSF-borne chemokines, extending the relevance of this migration pathway to neuroinflammatory and neuroinfectious disorders which are typified by elevated chemokine levels in CSF.
authors.affiliation: Brain-i, Lyon, France.|Blood-brain interfaces exploratory platform BIP and FLUID Team, Lyon Neurosciences Research Center, INSERM U1028 CRNS UMR 5292, Université Claude Bernard Lyon-1, Lyon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Strazielle
authors.affiliation: CRN2M, CNRS UMR 7286, Aix Marseille Univ, 13344, Marseille Cedex 15, France.|Plateforme de Biologie médicale, UF d'Immunologie, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
authors.forename: Rita
authors.initials: R
authors.lastname: Creidy
authors.affiliation: Service d'Immunologie, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Malcus
authors.affiliation: CRN2M, CNRS UMR 7286, Aix Marseille Univ, 13344, Marseille Cedex 15, France.
authors.forename: José
authors.initials: J
authors.lastname: Boucraut
authors.affiliation: Blood-brain interfaces exploratory platform BIP and FLUID Team, Lyon Neurosciences Research Center, INSERM U1028 CRNS UMR 5292, Université Claude Bernard Lyon-1, Lyon, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Ghersi-Egea
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology*; D002465:Cell Movement; D002555:Cerebrospinal Fluid / Q000276:immunology*; D002831:Choroid Plexus / Q000378:metabolism*; D057167:Claudins / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D018613:Microscopy, Confocal; D008954:Models, Biological; D051381:Rats; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D019108:Tight Junctions / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration
chemical_list: D057167:Claudins; D019707:Receptors, Chemokine