Tissue-resident memory T cells populate the human brain

被引：278

作者：

Smolders, Joost ^{[1
,2
]}

Heutinck, Kirstin M. ^{[3
]}

Fransen, Nina L. ^{[1
]}

Remmerswaal, Ester B. M. ^{[3
,4
]}

Hombrink, Pleun ^{[5
]}

ten Berge, Ineke J. M. ^{[3
,4
]}

van Lier, Rene A. W. ^{[5
]}

Huitinga, Inge ^{[1
]}

Hamann, Jorg ^{[1
,3
]}

机构：

[1] Netherlands Inst Neurosci, Dept Neuroimmunol, Meibergdreef 47, NL-1105 BA Amsterdam, Netherlands

[2] Canisius Wilhelmina Hosp, Dept Neurol, Weg Door Jonkerbos 100, NL-6532 SZ Nijmegen, Netherlands

[3] Univ Amsterdam, Amsterdam UMC, Amsterdam Infect & Immun Inst, Dept Expt Immunol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[4] Univ Amsterdam, Amsterdam UMC, Amsterdam Infect & Immun Inst, Renal Transplant Unit,Dept Internal Med, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[5] Univ Amsterdam, Amsterdam UMC, Amsterdam Infect & Immun Inst, Dept Hematopoiesis,Sanquin Res & Landsteiner Lab, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

COLONY-STIMULATING FACTOR; MULTIPLE-SCLEROSIS; GM-CSF; CYTOTOXIC FUNCTION; CNS DEMYELINATION; HUMAN NEURONS; EMERGING ROLE; CD8(+); EXPRESSION; INFECTION;

D O I：

10.1038/s41467-018-07053-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 69 条

[1] Functional maturation of adult mouse resting microglia into an APC is promoted by granulocyte-macrophage colony-stimulating factor and interaction with Th1 cells [J].