title: Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection.
abstract: Tissue-resident memory T cells (TRM) persist at sites of prior infection and have been shown to enhance pathogen clearance by recruiting circulating immune cells and providing bystander activation. Here, we characterize the functioning of brain-resident memory T cells (bTRM) in an animal model of viral infection. bTRM were subject to spontaneous homeostatic proliferation and were largely refractory to systemic immune cell depletion. After viral reinfection in mice, bTRM rapidly acquired cytotoxic effector function and prevented fatal brain infection, even in the absence of circulating CD8(+) memory T cells. Presentation of cognate antigen on MHC-I was essential for bTRM-mediated protective immunity, which involved perforin- and IFN-γ-dependent effector mechanisms. These findings identify bTRM as an organ-autonomous defense system serving as a paradigm for TRM functioning as a self-sufficient first line of adaptive immunity.
authors.affiliation: Departement de Pathologie et Immunologie, Centre Medical Universitaire, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Karin
authors.identifier: 0000-0001-9962-7994
authors.initials: K
authors.lastname: Steinbach
authors.affiliation: Departement de Pathologie et Immunologie, Centre Medical Universitaire, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Ilena
authors.initials: I
authors.lastname: Vincenti
authors.affiliation: Departement de Pathologie et Immunologie, Centre Medical Universitaire, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Mario
authors.identifier: 0000-0003-0335-2733
authors.initials: M
authors.lastname: Kreutzfeldt
authors.affiliation: Departement de Pathologie et Immunologie, Centre Medical Universitaire, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Nicolas
authors.identifier: 0000-0002-5845-6831
authors.initials: N
authors.lastname: Page
authors.affiliation: Klinikum rechts der Isar, Department of Experimental Neuroimmunology, Technical University of Munich, 81675 Munich, Germany.
authors.forename: Andreas
authors.identifier: 0000-0002-6870-1378
authors.initials: A
authors.lastname: Muschaweckh
authors.affiliation: Departement de Pathologie et Immunologie, Centre Medical Universitaire, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Wagner
authors.affiliation: Institute of Virology, University Hospital Düsseldorf, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
authors.forename: Ingo
authors.identifier: 0000-0002-6903-9144
authors.initials: I
authors.lastname: Drexler
authors.affiliation: Department of Biomedicine, University of Basel, 4056 Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pinschewer
authors.affiliation: Klinikum rechts der Isar, Department of Experimental Neuroimmunology, Technical University of Munich, 81675 Munich, Germany Munich Cluster of Systems Neurology (SyNergy), 81377 Munich, Germany.
authors.forename: Thomas
authors.identifier: 0000-0002-3633-0955
authors.initials: T
authors.lastname: Korn
authors.affiliation: Departement de Pathologie et Immunologie, Centre Medical Universitaire, University of Geneva, 1211 Geneva, Switzerland Division of Clinical Pathology, Geneva University Hospital, 1211 Geneva, Switzerland doron.merkler@unige.ch.
authors.forename: Doron
authors.identifier: 0000-0002-0247-2007
authors.initials: D
authors.lastname: Merkler
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: C000611649:IFNG protein, mouse; D007371:Interferon-gamma