title: Central Nervous System Stromal Cells Control Local CD8(+) T Cell Responses during Virus-Induced Neuroinflammation.
abstract: Stromal cells generate a complex cellular scaffold that provides specialized microenvironments for lymphocyte activation in secondary lymphoid organs. Here, we assessed whether local activation of stromal cells in the central nervous system (CNS) is mandatory to transfer immune recognition from secondary lymphoid organs into the infected tissue. We report that neurotropic virus infection in mice triggered the establishment of such stromal cell niches in the CNS. CNS stromal cell activation was dominated by a rapid and vigorous production of CC-motif chemokine receptor (CCR) 7 ligands CCL19 and CCL21 by vascular endothelial cells and adjacent fibroblastic reticular cell (FRC)-like cells in the perivascular space. Moreover, CCR7 ligands produced by CNS stromal cells were crucial to support recruitment and local re-activation of antiviral CD8(+) T cells and to protect the host from lethal neuroinflammatory disease, indicating that CNS stromal cells generate confined microenvironments that control protective T cell immunity.
authors.affiliation: Institute for Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.
authors.forename: Jovana
authors.initials: J
authors.lastname: Cupovic
authors.affiliation: Institute for Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.
authors.forename: Lucas
authors.initials: L
authors.lastname: Onder
authors.affiliation: Institute for Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gil-Cruz
authors.affiliation: Institute of Anatomy, University of Leipzig, 04103 Leipzig, Germany; Institute for Neurobiology, University of Ulm, 89081 Ulm, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Weiler
authors.affiliation: Institute for Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.
authors.forename: Sonja
authors.initials: S
authors.lastname: Caviezel-Firner
authors.affiliation: Institute for Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Perez-Shibayama
authors.affiliation: Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rülicke
authors.affiliation: Institute of Anatomy, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Bechmann
authors.affiliation: Institute for Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland. Electronic address: burkhard.ludewig@kssg.ch.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D060833:Cellular Microenvironment; D002490:Central Nervous System / Q000276:immunology* / Q000821:virology; D054415:Chemokine CCL19 / Q000378:metabolism; D054421:Chemokine CCL21 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology* / Q000821:virology; D006506:Hepatitis A / Q000150:complications / Q000276:immunology*; D030041:Hepatitis A virus / Q000276:immunology*; D007111:Immunity, Cellular; D056747:Immunomodulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020078:Neurogenic Inflammation / Q000209:etiology / Q000469:parasitology*; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000276:immunology* / Q000821:virology; D056189:Viral Tropism
chemical_list: C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054400:Receptors, CCR7
keywords: Inflammation; encephalitis; stromal cells; virus infection