Microglia require CD4 T cells to complete the fetal to adult transition

The blood brain barrier has long been thought to isolate the brain from the adaptive immune system. While CD4 T cells have been reported in the central nervous system, their presence in the healthy brain remains controversial, and their function at this site unknown. Here we have used a combination of imaging, single cell and surgical approaches to identify a unique CD69+ CD4 T cell population in both the mouse and human brain, which is distinct from circulating CD4 T cells. The brain-resident population was derived through in situ differentiation from activated circulatory cells, and was shaped by interaction with the gut microbiome and self-antigen in the brain. Single cell sequencing revealed that in the absence of murine CD4 T cells, resident microglia remained suspended between a fetal and adult state. This maturation defect resulted in excess immature neuronal synapses and behavioral abnormalities in the adult mouse. These results illuminate a role for CD4 T cells in the basic developmental processes of the brain, and a potential interconnected dynamic between the evolution of the immunological and neurological systems. Quantification and characterisation of the brain CD4 T cell population in two wild type mice and one MHC class II-deficient mouse with a near-complete absence of CD4 T cells

血脑屏障（Blood Brain Barrier）长期以来被认为可将大脑与适应性免疫系统分隔开来。尽管已有研究在中枢神经系统（Central Nervous System）中报道过CD4 T细胞（CD4 T cells）的存在，但其在健康大脑中的出现仍存在争议，且其在该部位的功能尚未明确。本研究结合成像技术、单细胞技术与手术方法，在小鼠与人类大脑中鉴定出一类独特的CD69+ CD4 T细胞群，该群体与循环CD4 T细胞截然不同。这类脑驻留群体由活化的循环细胞在原位分化而来，并受肠道菌群与大脑内自身抗原的相互作用塑造。单细胞测序（Single Cell Sequencing）结果显示，在缺乏小鼠CD4 T细胞的情况下，驻留小胶质细胞（Microglia）会停滞在胎儿态与成人态之间。这种成熟缺陷会导致成年小鼠出现过多的未成熟神经元突触与行为异常。上述研究结果阐明了CD4 T细胞在大脑基本发育过程中的关键作用，以及免疫系统与神经系统演化之间潜在的互作动态。本研究对两只野生型小鼠与一只几乎完全缺失CD4 T细胞的主要组织相容性复合体II类（MHC class II）缺陷型小鼠的脑CD4 T细胞群体进行了定量分析与特征表征。