A genetic and functional relationship between T cells and cellular proliferation in the adult hippocampus

Guo Jen Huang; Adrian L. Smith; Daniel H.D. Gray; Cormac Cosgrove; Benjamin H. Singer; Andrew Edwards; Stuart Sim; Jack M. Parent; Alyssa Johnsen; Richard Mott; Diane Mathis; Paul Klenerman; Christophe Benoist; Jonathan Flint

doi:10.1371/journal.pbio.1000561

A genetic and functional relationship between T cells and cellular proliferation in the adult hippocampus

Guo Jen Huang, Adrian L. Smith, Daniel H.D. Gray, Cormac Cosgrove, Benjamin H. Singer, Andrew Edwards, Stuart Sim, Jack M. Parent, Alyssa Johnsen, Richard Mott, Diane Mathis, Paul Klenerman, Christophe Benoist, Jonathan Flint^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

30 Scopus citations

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 TCRa-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 language	English
Article number	e1000561
Journal	PLoS Biology
Volume	8
Issue number	12
DOIs	https://doi.org/10.1371/journal.pbio.1000561
State	Published - 12 2010
Externally published	Yes

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Huang, G. J., Smith, A. L., Gray, D. H. D., Cosgrove, C., Singer, B. H., Edwards, A., Sim, S., Parent, J. M., Johnsen, A., Mott, R., Mathis, D., Klenerman, P., Benoist, C., & Flint, J. (2010). A genetic and functional relationship between T cells and cellular proliferation in the adult hippocampus. PLoS Biology, 8(12), Article e1000561. https://doi.org/10.1371/journal.pbio.1000561

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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 TCRa-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.",

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AU - Huang, Guo Jen

AU - Smith, Adrian L.

AU - Gray, Daniel H.D.

AU - Cosgrove, Cormac

AU - Singer, Benjamin H.

AU - Edwards, Andrew

AU - Sim, Stuart

AU - Parent, Jack M.

AU - Johnsen, Alyssa

AU - Mott, Richard

AU - Mathis, Diane

AU - Klenerman, Paul

AU - Benoist, Christophe

AU - Flint, Jonathan

PY - 2010/12

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AB - 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 TCRa-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.

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A genetic and functional relationship between T cells and cellular proliferation in the adult hippocampus

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