title: Brain antigen-reactive CD4+ T cells are sufficient to support learning behavior in mice with limited T cell repertoire.
abstract: Numerous methods of T cell depletion lead to impairment of learning and memory function in mice. While adoptive transfer of whole splenocytes rescues learning behavior impairments, the precise sub-population and antigenic specificity of the T cells mediating the rescue remains unknown. Using several transgenic mouse models in combination with adoptive transfers, we demonstrate the necessity of an antigen-specific CD4(+) T cell compartment in normal spatial learning and memory, as measured by the Morris water maze (MWM). Moreover, transfer of a monoclonal T cell population reactive to the central nervous system (CNS) antigen, myelin oligodendrocyte glycoprotein (MOG), was sufficient to improve cognitive task performance in otherwise impaired OTII mice, raising the possibility that the antigen-specificity requirement of pro-cognitive T cells may be directed against CNS-derived self-antigens.
authors.affiliation: Center for Brain Immunology and Glia (BIG), Department of Neuroscience, University of Virginia, Charlottesville, VA 22908, USA; Immunology Graduate Program, University of Virginia, Charlottesville, VA 22908, USA; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Radjavi
authors.forename: Igor
authors.initials: I
authors.lastname: Smirnov
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kipnis
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005802:Genes, MHC Class II; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse
keywords: 2D2 mice; Antigen specificity; CD4 T cells; Learning behavior; Meningeal immunity; Morris water maze; OTII mice; Pro-cognitive T cells