title: CD11c-Expressing Cells Affect Regulatory T Cell Behavior in the Meninges during Central Nervous System Infection.
abstract: Regulatory T cells (Tregs) play an important role in the CNS during multiple infections, as well as autoimmune inflammation, but the behavior of this cell type in the CNS has not been explored. In mice, infection withToxoplasma gondiileads to a Th1-polarized parasite-specific effector T cell response in the brain. Similarly, Tregs in the CNS duringT. gondiiinfection are Th1 polarized, as exemplified by their T-bet, CXCR3, and IFN-γ expression. Unlike effector CD4+T cells, an MHC class II tetramer reagent specific forT. gondiidid not recognize Tregs isolated from the CNS. Likewise, TCR sequencing revealed minimal overlap in TCR sequence between effector T cells and Tregs in the CNS. Whereas effector T cells are found in the brain parenchyma where parasites are present, Tregs were restricted to the meninges and perivascular spaces. The use of intravital imaging revealed that activated CD4+T cells within the meninges were highly migratory, whereas Tregs moved more slowly and were found in close association with CD11c+cells. To test whether the behavior of Tregs in the meninges is influenced by interactions with CD11c+cells, mice were treated with anti-LFA-1 Abs to reduce the number of CD11c+cells in this space. The anti-LFA-1 treatment led to fewer contacts between Tregs and the remaining CD11c+cells and increased the speed of Treg migration. These data suggest that Tregs are anatomically restricted within the CNS, and their interaction with CD11c+populations regulates their local behavior duringT. gondiiinfection.
authors.affiliation: Center for Brain Immunology and Glia, Department of Neuroscience, University of Virginia, Charlottesville, VA 22908; and.
authors.forename: Carleigh A
authors.initials: CA
authors.lastname: O'Brien
authors.affiliation: Center for Brain Immunology and Glia, Department of Neuroscience, University of Virginia, Charlottesville, VA 22908; and.
authors.forename: Christopher
authors.initials: C
authors.lastname: Overall
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Christoph
authors.initials: C
authors.lastname: Konradt
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Aisling C
authors.initials: AC
authors.lastname: O'Hara Hall
authors.affiliation: Center for Brain Immunology and Glia, Department of Neuroscience, University of Virginia, Charlottesville, VA 22908; and.
authors.forename: Nikolas W
authors.identifier: 0000-0003-1885-1850
authors.initials: NW
authors.lastname: Hayes
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Sagie
authors.initials: S
authors.lastname: Wagage
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Beena
authors.initials: B
authors.lastname: John
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: David A
authors.initials: DA
authors.lastname: Christian
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hunter
authors.affiliation: Center for Brain Immunology and Glia, Department of Neuroscience, University of Virginia, Charlottesville, VA 22908; and tajieharris@virginia.edu.
authors.forename: Tajie H
authors.initials: TH
authors.lastname: Harris
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D000069416:Intravital Microscopy; D008213:Lymphocyte Activation; D008578:Meninges / Q000276:immunology*; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology; D016781:Toxoplasmosis, Cerebral / Q000276:immunology*
chemical_list: D039521:CD11c Antigen; D011948:Receptors, Antigen, T-Cell