TY - JOUR
T1 - Tissue-resident memory T cells populate the human brain
AU - Smolders, Joost
AU - Heutinck, Kirstin M.
AU - Fransen, Nina L.
AU - Remmerswaal, Ester B.M.
AU - Hombrink, Pleun
AU - ten Berge, Ineke J.M.
AU - van Lier, René A.W.
AU - Huitinga, Inge
AU - Hamann, Jörg
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/11/2
Y1 - 2018/11/2
N2 - Most tissues are populated by tissue-resident memory T cells (T RM 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 T RM 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 T RM cell-associated markers but have low CD103 expression. We conclude that the human brain is surveilled by T RM cells, providing protection against neurotropic virus reactivation, whilst being under tight control of key immune checkpoint molecules.
AB - Most tissues are populated by tissue-resident memory T cells (T RM 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 T RM 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 T RM cell-associated markers but have low CD103 expression. We conclude that the human brain is surveilled by T RM cells, providing protection against neurotropic virus reactivation, whilst being under tight control of key immune checkpoint molecules.
UR - http://www.scopus.com/inward/record.url?scp=85055966401&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-07053-9
DO - 10.1038/s41467-018-07053-9
M3 - Article
C2 - 30389931
AN - SCOPUS:85055966401
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4593
ER -