Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, CENTRAL-NERVOUS-SYSTEM, IMMUNE CELLS, MOUSE MODEL, BRAIN, MICE, MEMORY, ABNORMALITIES, LYMPHOCYTES, DEFICITS, SCHIZOPHRENIA, CD4 T cells, T cells, brain, differentiation, human, microflora, microglia, migration, mouse, tissue-resident, Adult, Animals, Antigens, CD, Antigens, Differentiation, T-Lymphocyte, Behavior Rating Scale, Blood Cells, Brain, CD4-Positive T-Lymphocytes, Child, Female, Fetus, Humans, Lectins, C-Type, Lung, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microglia, Middle Aged, Neurogenesis, Parabiosis, Pyramidal Cells, Single-Cell Analysis, Spleen, Synapses, Transcriptome, G0B9219N#54969401, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 31 Biological sciences, 32 Biomedical and clinical sciences

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.