Completed Infection & Immunity Brain & Nervous System

Brain CD4 T cells and their influence over microglial homeostasis

Funder Wellcome Charity-funded
Recipient organisation Babraham Institute
Funding £1.9M
Period Jul 2021 — Jun 2026

In plain English

AI plain-English summary

Immune cells from the body briefly take up residence in the brain shortly after birth, where they help shape the brain’s own immune cells into their mature form. This discovery, made by the applicants, upends the long-held view that the brain is entirely sealed off from the body’s immune system. It raises a fundamental question: what else do these visiting T cells do? The team has now developed three new tools to find out. They will track how T cells enter the brain and adopt a brain-specific identity, use a genetic trick to see how microglia sense and respond to T cells, and follow individual microglial cells over time to see whether T-cell interactions alter their behaviour during ageing or after a head injury. This is fundamental science. It will not produce a treatment or diagnostic tomorrow. But it fills a major gap in our understanding of how the brain’s immune system works—a system increasingly linked to dementia, traumatic brain injury, and neurodevelopmental conditions. The tools themselves, particularly the competitive chimeric analysis method, could be adapted by other labs studying cell interactions in any tissue.

View original technical description
Microglia are the main immunological cell of the brain. These residential cells possess both immunological and neurodevelopmental functions, and have pathological roles during age- and injury-associated dementia. We recently characterised a new addition to the neuroimmunological landscape: transiently-resident brain CD4 T cells. Brain T cells are required to trigger the post-natal differentiation of foetal microglia, licensing their neurodevelopmental functions. Much remains unknown about potential further interactions between brain CD4 T cells and microglia. We have adapted cutting-edge technology to enable the parallel study of brain CD4 T cells and microglia. First, will use an adapted flow-based ProCode approach to unravel the molecular control over CD4 T cell entry to the brain and acquisition of the residential phenotype. Second, we have developed a novel genetic tool for competitive chimeric analysis, allowing us to study microglia niche-sensing and the role of interaction with CD4 T cells on microgliosis. Third, we will single cell lineage tracing to dissect the clonal evolution of microglia, and the influence of CD4 T cell interaction on microglial clonal dominance during ageing and following traumatic brain injury. The results will generate new insight into neuroimmune inter-cellular dynamics, and will validate new tools with broad applicability to biomedical sciences.

View the original record at the funder ↗

Researchers

Adrian Liston (EPMC Awardee)

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Original classification

Investigator Award in Science

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