title: A genetic and functional relationship between T cells and cellular proliferation in the adult hippocampus.
abstract: Neurogenesis continues through the adult life of mice in the subgranular zone of the dentate gyrus in the hippocampus, but its function remains unclear. Measuring cellular proliferation in the hippocampus of 719 outbred heterogeneous stock mice revealed a highly significant correlation with the proportions of CD8+ versus CD4+ T lymphocyte subsets. This correlation reflected shared genetic loci, with the exception of the H-2Ea locus that had a dominant influence on T cell subsets but no impact on neurogenesis. Analysis of knockouts and repopulation of TCRα-deficient mice by subsets of T cells confirmed the influence of T cells on adult neurogenesis, indicating that CD4+ T cells or subpopulations thereof mediate the effect. Our results reveal an organismal impact, broader than hitherto suspected, of the natural genetic variation that controls T cell development and homeostasis.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Guo-Jen
authors.initials: GJ
authors.lastname: Huang
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Smith
authors.forename: Daniel H D
authors.initials: DH
authors.lastname: Gray
authors.forename: Cormac
authors.initials: C
authors.lastname: Cosgrove
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Singer
authors.forename: Andrew
authors.initials: A
authors.lastname: Edwards
authors.forename: Stuart
authors.initials: S
authors.lastname: Sims
authors.forename: Stuart
authors.initials: S
authors.lastname: Sim
authors.forename: Jack M
authors.initials: JM
authors.lastname: Parent
authors.forename: Alyssa
authors.initials: A
authors.lastname: Johnsen
authors.forename: Richard
authors.initials: R
authors.lastname: Mott
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D049109:Cell Proliferation; D014644:Genetic Variation; D006624:Hippocampus / Q000166:cytology* / Q000276:immunology; D019394:Ki-67 Antigen / Q000235:genetics / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D055495:Neurogenesis; D040641:Quantitative Trait Loci; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology
chemical_list: D019394:Ki-67 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta