Cited by 329Neurogenesis and neuroplasticity mechanismsNeuroinflammation and Neurodegeneration MechanismsT-cell and B-cell Immunology

CD4-positive T lymphocytes provide a neuroimmunological link in the control of adult hippocampal neurogenesis

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Wolf, Susanne A, Steiner, Barbara, Akpinarli, Akgul, Kammertoens, Thomas, Nassenstein, Christina, Braun, Armin, Blankenstein, Thomas, Kempermann, Gerd·2009·The Journal of Immunology

Abstract

Adult hippocampal neurogenesis occurs in an exceptional permissive microenvironment. Neuroimmunological mechanisms might be prominently involved in the endogenous homeostatic principles that control baseline levels of adult neurogenesis. We show in this study that this homeostasis is partially dependent on CD4-positive T lymphocytes. Systemic depletion of CD4-positive T lymphocytes led to significantly reduced hippocampal neurogenesis, impaired reversal learning in the Morris water maze, and decreased brain-derived neurotrophic factor expression in the brain. No such effect of CD8 or B cells was observed. Repopulation of RAG2−/− mice with CD4, but not with CD8 cells again increased precursor cell proliferation. The T cells in our experiments were non-CNS specific and rarely detectable in the healthy brain. Thus, we can exclude cell-cell contacts between immune and brain cells or lymphocyte infiltration into the CNS as a prerequisite for an effect of CD4-T cells on neurogenesis. We propose that systemic CD4-T cell activity is required for maintaining cellular plasticity in the adult hippocampus and represents an evolutionary relevant communication route for the brain to respond to environmental changes.

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  • CD4+ T cells are necessary for hippocampal neurogenesis in adult rodents.

    “CD4+ T cells are necessary for hippocampal neurogenesis in adult rodents”

    From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [28]

    The Abstract and Discussion report that CD4+ T-cell depletion reduces adult hippocampal neurogenesis in mice, supporting a role in maintaining its baseline level. But the Discussion also says neurogenesis remained at low levels in CD4-depleted and CD4-knockout mice and could still increase with running. Thus, the paper does not establish that CD4+ T cells are necessary for neurogenesis to occur. Page numbers were not provided in our copy. (LLM, conf=0.88)

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Authors
Wolf, S. A., Steiner, B., Akpinarli, A., Kammertoens, T., Nassenstein, C., Braun, A., Blankenstein, T., & Kempermann, G.
Affiliations
  • University of Zurich (CH)
  • Max Delbrück Center (DE)
  • National Institutes of Health, National Institute of Allergy and Infectious Diseases, Laboratory of Cellular and Molecular Immunology , Bethesda, MD
  • Fraunhofer Institute for Toxicology and Experimental Medicine (DE)
Corresponding author
  • Steiner, Barbara
  • Kempermann, Gerd
Venue
The Journal of Immunology
Published
2009-04-01
Volume
182
Issue
7
Pages
3979-3984
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W2109261715
Cited by
329
References
47
Citations by year
2026: 8 · 2025: 26 · 2024: 15 · 2023: 25 · 2022: 15 · 2021: 25 · 2020: 11 · 2019: 20 · 2018: 18 · 2017: 17 · 2016: 28 · 2015: 21 · 2014: 23 · 2013: 16 · 2012: 20
FWCI
6.38
Type
journal article
Language
en
Open access
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion)
  • Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
adult hippocampal neurogenesis, CD4-positive T lymphocytes, neuroimmunology, reversal learning, brain-derived neurotrophic factor, CD8+ T cells, B cells, Rag2 knockout mice, neural progenitor proliferation, hippocampal plasticity
MeSH terms
Animals, B-Lymphocytes, DNA-Binding Proteins, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Fluorescent Antibody Technique, Hippocampus, Immunohistochemistry, Mice, Inbred C57BL, CD4-Positive T-Lymphocytes, T-Lymphocyte Subsets, Mice, Knockout, Maze Learning, Cell Proliferation, Mice, Neurogenesis

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