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

Abstract

Summary 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

A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice

“…Manual gating of flow cytometry data was done using FlowJo v10 software (Tree Star). tSNE, FlowSOM and heatmap analysis were performed on iLN samples from day 7 post-vaccination using R (version 4.0.2) using code that has previously been described 56 . The antibodies used for surface staining are listed in Key Resources Table .…”

The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology

“…Within the first three months of life in humans, its size increases more than 50% from the time of birth, reaching 90% of the size of the adult organ within the first five years of life (72). In this period, neuronal development takes place (73) and it is supported and shaped by maternal microbiota (74)(75)(76)(77)(78)(79).…”

The aryl hydrocarbon receptor and the gut–brain axis

“…98,99 In addition, recruited T cells secrete cytokines that modulate the activity of CNS-resident immune cells, such as microglia and astrocytes. [100][101][102] In pioneering studies, Wekerle and coworkers demonstrated that the commensal gut flora controls autoreactive T cells that migrate to the CNS and cause inflammation and tissue pathology. 103 Follow-up studies defined alterations in the gut microbiota associated with MS 104 and identified specific components of the microbiome involved in the regulation of effector and regulatory T cells.…”