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Tissue-resident memory T cells populate the human brain

Author

Listed:
  • Joost Smolders

    (Netherlands Institute for Neuroscience
    Canisius Wilhelmina Hospital)

  • Kirstin M. Heutinck

    (University of Amsterdam)

  • Nina L. Fransen

    (Netherlands Institute for Neuroscience)

  • Ester B. M. Remmerswaal

    (University of Amsterdam
    University of Amsterdam)

  • Pleun Hombrink

    (University of Amsterdam)

  • Ineke J. M. Berge

    (University of Amsterdam
    University of Amsterdam)

  • René A. W. Lier

    (University of Amsterdam)

  • Inge Huitinga

    (Netherlands Institute for Neuroscience)

  • Jörg Hamann

    (Netherlands Institute for Neuroscience
    University of Amsterdam)

Abstract

Most tissues are populated by tissue-resident memory T cells (TRM cells), which are adapted to their niche and appear to be indispensable for local protection against pathogens. Here we show that human white matter-derived brain CD8+ T cells can be subsetted into CD103−CD69+ and CD103+CD69+ T cells both with a phenotypic and transcription factor profile consistent with TRM cells. Specifically, CD103 expression in brain CD8+ T cells correlates with reduced expression of differentiation markers, increased expression of tissue-homing chemokine receptors, intermediate and low expression of the transcription factors T-bet and eomes, increased expression of PD-1 and CTLA-4, and low expression of cytolytic enzymes with preserved polyfunctionality upon activation. Brain CD4+ T cells also display TRM cell-associated markers but have low CD103 expression. We conclude that the human brain is surveilled by TRM cells, providing protection against neurotropic virus reactivation, whilst being under tight control of key immune checkpoint molecules.

Suggested Citation

  • Joost Smolders & Kirstin M. Heutinck & Nina L. Fransen & Ester B. M. Remmerswaal & Pleun Hombrink & Ineke J. M. Berge & René A. W. Lier & Inge Huitinga & Jörg Hamann, 2018. "Tissue-resident memory T cells populate the human brain," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07053-9
    DOI: 10.1038/s41467-018-07053-9
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    Cited by:

    1. Nicola A. Kearns & Artemis Iatrou & Daniel J. Flood & Sashini Tissera & Zachary M. Mullaney & Jishu Xu & Chris Gaiteri & David A. Bennett & Yanling Wang, 2023. "Dissecting the human leptomeninges at single-cell resolution," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Gao, Qishuo & Shi, Vivien & Pettit, Christopher & Han, Hoon, 2022. "Property valuation using machine learning algorithms on statistical areas in Greater Sydney, Australia," Land Use Policy, Elsevier, vol. 123(C).
    3. John Chulhoon Park & Min-A Sim & Changhon Lee & Hye-Eun Park & Juhun Lee & Seung Yeon Choi & Seohyun Byun & Haeun Ko & Haena Lee & Seung Won Kim & Jaegyun Noh & Geon Park & Solji Lee & Tae-Kyung Kim &, 2025. "Gut microbiota and brain-resident CD4+ T cells shape behavioral outcomes in autism spectrum disorder," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    4. Eleonora Terrabuio & Enrica Caterina Pietronigro & Alessandro Bani & Vittorina Bianca & Carlo Laudanna & Barbara Rossi & Giulia Finotti & Bruno Santos-Lima & Elena Zenaro & Ermanna Turano & Gabriele T, 2025. "CD103–CD8+ T cells promote neurotoxic inflammation in Alzheimer’s disease via granzyme K–PAR-1 signaling," Nature Communications, Nature, vol. 16(1), pages 1-24, December.
    5. Manisha Menon & Colin N. Haile & David J. Dowling, 2025. "Incorporating meningeal immunity into vaccine development," Nature Communications, Nature, vol. 16(1), pages 1-8, December.
    6. Hu, Maggie R. & Lee, Adrian D. & Zou, Dihan, 2021. "COVID-19 and Housing Prices: Australian Evidence with Daily Hedonic Returns," Finance Research Letters, Elsevier, vol. 43(C).
    7. Maxwell Ma & Fahad Paryani & Kelly Jakubiak & Shengnan Xia & Susumu Antoku & Adithya Kannan & Jaeseung Lee & Nacoya Madden & Shailesh Senthil Kumar & Juncheng Li & David Chen & Gunnar Hargus & Aayushi, 2025. "The spatial landscape of glial pathology and T cell response in Parkinson’s disease substantia nigra," Nature Communications, Nature, vol. 16(1), pages 1-24, December.

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