Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition
Authors: Raul Y Tito
Renzo Mancuso
Anna Martinez-Muriana
James Dooley
Pierre Lemaitre
Michelle Naughton
Aleksandra Brajic
Andrew Young
Zsuzsanna Callaerts-Vegh
Oliver T Burton
Tom Theys
Lidia Yshii
Denise C Fitzgerald
Lubna Kouser
Carly E Whyte
Vasiliki Lagou
Jeroen Raes
Loriana G Mascali
Alena Moudra
Alerie G de la Fuente
Suresh Poovathingal
Emanuela Pasciuto
Bart De Strooper
Teresa Prezzemolo
Carlos P Roca
Wenson D Rajan
Adrian Liston
Journal: Cell (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CD4 T cells; T cells; brain; differentiation; human
Affiliations: VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium., Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK., Department of Neurosurgery, UZ Leuven, Leuven 3000, Belgium., VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Neurosciences, KU Leuven-University of Leuven, Leuven 3000, Belgium., Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium; VIB-KU Leuven Center for Microbiology, VIB, Leuven 3000, Belgium., Department of Brain and Cognition, KU Leuven-University of Leuven, Leuven 3000, Belgium., The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast BT7 1NN, UK., VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium., VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Neurosciences, KU Leuven-University of Leuven, Leuven 3000, Belgium; Dementia Research Institute, University College London, London WC1E 6BT, UK., VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium; Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, UK. Electronic address: .

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. 

Retracted: No

PubPeer comments:
 Fig. 2H: this is a volcano plot of differentially expressed genes in sorted CD4 T cells from human brain *vs*. PBMC. Two among the most differentially expressed genes are *XIST* (downregulated) and *RPS4Y1* (upregulated). These genes are localized on the X and Y chromosome, respectively. Their differential expression is most likely determined by skewed use of male and female samples in those experiments and strongly suggests that PBMC samples were prevalently derived from male individuals while brain samples were from females, *i.e*. individuals from whom brain samples were taken were different from individuals from whom blood samples were taken (brain-blood mismatch). Differential gene expression in brain *vs*. blood CD4 T populations may then simply reflect sex-related differences and or be related to the pathologies affecting patients from whom brain samples were taken. ,