Immune cells guide T cells into the ageing brain

The blood-brain barrier keeps most immune cells out. But a subset of white blood cells called T cells can cross it. As the barrier becomes leakier with age, more T cells enter the brain. This appears to worsen conditions like Alzheimer’s disease. Until now, it was unclear what triggers T cells to make that crossing.

Researchers have now identified the key intermediary: specialised immune cells in the body known as dendritic cells. These cells present targets to T cells outside the brain, essentially priming them to seek out and attack brain tissue. The researchers used mice engineered to overproduce tau protein, which clumps together in Alzheimer’s and related conditions.

Removing dendritic cells reduces brain damage in mice

When dendritic cells were genetically eliminated in these mice, the damaging effects of T cells inside the brain were substantially reduced. Tau-related neurodegeneration, the progressive loss of nerve cells driven by aggregated tau protein, was noticeably diminished. This suggests that dendritic cell activation is a step that could, in principle, be therapeutically interrupted.

The study also addresses a broader question in ageing research: how do the body’s peripheral immune system and the brain’s immune system interact as we age? Inflammatory activity in the brain (neuroinflammation) increases with age, and some of that activity appears to be driven by signals originating outside the brain. The study focuses specifically on CD8+ T cells, a type of T cell capable of killing cells it recognises as damaged or threatening.

No clinical translation yet

This is an animal study. Eliminating dendritic cells is not a realistic therapy, as these cells are essential for overall immune defence. But pinpointing the specific step at which dendritic cells prime T cells for brain migration offers a more precise target for future research into immunotherapy for neurodegenerative disease.

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