Tissue-resident memory T cells populate the human brain

Joost Smolders (), Kirstin M. Heutinck, Nina L. Fransen, Ester B. M. Remmerswaal, Pleun Hombrink, Ineke J. M. Berge, René A. W. Lier, Inge Huitinga and Jörg Hamann ()
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Joost Smolders: Netherlands Institute for Neuroscience
Kirstin M. Heutinck: University of Amsterdam
Nina L. Fransen: Netherlands Institute for Neuroscience
Ester B. M. Remmerswaal: University of Amsterdam
Pleun Hombrink: University of Amsterdam
Ineke J. M. Berge: University of Amsterdam
René A. W. Lier: University of Amsterdam
Inge Huitinga: Netherlands Institute for Neuroscience
Jörg Hamann: Netherlands Institute for Neuroscience

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07053-9

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