Journal
CELL
Volume 182, Issue 3, Pages 625-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2020.06.026
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Categories
Funding
- VIB
- Rega Institute
- ERC Consolidator Grant TissueTreg
- Alzheimer's Association Research Grant
- ERC
- Biotechnology and Biological Sciences Research Council (BBSRC) [BBS/E/B/000C0427, BBS/E/B/000C0428]
- BBSRC Core Capability Grant
- FWO
- AARF
- KUL
- BBSRC [BBS/E/B/000C0427] Funding Source: UKRI
- MRC [UKDRI-1004] Funding Source: UKRI
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The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains controversial, and their function remains largely unknown. We used a combination of imaging, single cell, and surgical approaches to identify a CD69(+) CD4 T cell population in both the mouse and human brain, distinct from circulating CD4 T cells. The brain-resident population was derived through in situ differentiation from activated circulatory cells and was shaped by self-antigen and the peripheral microbiome. Single-cell sequencing revealed that in the absence of murine CD4 T cells, resident microglia remained suspended between the fetal and adult states. This maturation defect resulted in excess immature neuronal synapses and behavioral abnormalities. These results illuminate a role for CD4 T cells in brain development and a potential interconnected dynamic between the evolution of the immunological and neurological systems.
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