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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.

Original publication

DOI

10.1371/journal.pbio.1000561

Type

Journal article

Journal

PLoS Biol

Publication Date

14/12/2010

Volume

8

Keywords

Animals, Animals, Outbred Strains, CD4-CD8 Ratio, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Proliferation, Genetic Variation, Hippocampus, Ki-67 Antigen, Mice, Mice, Inbred Strains, Mutation, Neurogenesis, Quantitative Trait Loci, Receptors, Antigen, T-Cell, alpha-beta