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CD4-Positive T Lymphocytes Provide a Neuroimmunological Link in the Control of Adult Hippocampal Neurogenesis
Open accessAbstract
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”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [28]
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Metadata
- 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
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- 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
- bronze
- doi.org
- 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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