title: Th1 polarization of T cells injected into the cerebrospinal fluid induces brain immunosurveillance.
abstract: Although CD4 T cells reside within the cerebrospinal fluid, it is yet unclear whether and how they enter the brain parenchyma and migrate to target specific Ags. We examined the ability of Th1, Th2, and Th17 CD4 T cells injected intracerebroventricularly to migrate from the lateral ventricles into the brain parenchyma in mice. We show that primarily Th1 cells cross the ependymal layer of the ventricle and migrate within the brain parenchyma by stimulating an IFN-γ-dependent dialogue with neural cells, which maintains the effector function of the T cells. When injected into a mouse model of Alzheimer's disease, amyloid-β (Aβ)-specific Th1 cells target Aβ plaques, increase Aβ uptake, and promote neurogenesis with no evidence of pathogenic autoimmunity or neuronal loss. Overall, we provide a mechanistic insight to the migration of cerebrospinal fluid CD4 T cells into the brain parenchyma and highlight implications on brain immunity and repair.
authors.affiliation: Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Fisher
authors.forename: Itai
authors.initials: I
authors.lastname: Strominger
authors.forename: Shva
authors.initials: S
authors.lastname: Biton
authors.forename: Anna
authors.initials: A
authors.lastname: Nemirovsky
authors.forename: Rona
authors.initials: R
authors.lastname: Baron
authors.forename: Alon
authors.initials: A
authors.lastname: Monsonego
mesh_terms: D019264:Adoptive Transfer; D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000276:immunology; D000818:Animals; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D015166:Monitoring, Immunologic; D058225:Plaque, Amyloid; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018925:Chemokines