Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition

Emanuela Pasciuto, Oliver T Burton, Carlos P Roca, Vasiliki Lagou, Wenson D Rajan, Tom Theys, Renzo Mancuso, Raul Y Tito, Lubna Kouser, Zsuzsanna Callaerts-Vegh, Alerie G de la Fuente, Teresa Prezzemolo, Loriana G Mascali, Aleksandra Brajic, Carly E Whyte, Lidia Yshii, Anna Martinez-Muriana, Michelle Naughton, Andrew Young, Alena MoudraPierre Lemaitre, Suresh Poovathingal, Jeroen Raes, Bart De Strooper, Denise C Fitzgerald, James Dooley, Adrian Liston

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)
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Abstract

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. VIDEO ABSTRACT.

Original languageEnglish
Pages (from-to)625
JournalCell
Volume182
Issue number3
Early online date20 Jul 2020
DOIs
Publication statusEarly online date - 20 Jul 2020

Bibliographical note

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

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