Inflammatory T Cells Found in Cerebrospinal Fluid of Cognitive Impairment Patients
Inflammation in brain tissue is a feature of neurodegenerative conditions, and chronic inflammation is a feature of aging in general. This unresolved inflammatory signaling is disruptive to normal tissue structure and function. Researchers here note a consequence of inflammation in the innate immune cells of the brain, microglia. They produce a signal that draws in active, inflammatory T cells from the body in large numbers, which no doubt makes the situation worse. Normally there is little traffic between the separate immune systems of the brain and body, but the blood-brain barrier enforcing that separation becomes leaky with age, allowing inappropriate cells and molecules into brain tissue, where they can cause damage.
As people age, their cerebrospinal fluid (CSF) immune system becomes dysregulated. In people with cognitive impairment, such as those with Alzheimer's disease, the CSF immune system is drastically different from healthy individuals, a new study discovered. To analyze the CSF, researchers used single-cell RNA sequencing. They profiled 59 CSF immune systems from a spectrum of ages by taking CSF from participants' spines and isolating their immune cells. The first part of the study looked at CSF in 45 healthy individuals aged 54 to 83 years. The second part of the study compared those findings in the healthy group to CSF in 14 adults with cognitive impairment, as determined by their poor scores on memory tests.
Scientists observed genetic changes in the CSF immune cells in older healthy individuals that made the cells appear more activated and inflamed with advanced age. In the cognitively impaired group, inflamed T-cells cloned themselves and flowed into the CSF and brain. Scientists found the cells had an overabundance of a cell receptor - CXCR6 - that acts as an antenna. This receptor receives a signal - CXCL16 - from the degenerating brain's microglia cells to enter the brain. "It could be the degenerating brain activates these cells and causes them to clone themselves and flow to the brain. They do not belong there, and we are trying to understand whether they contribute to damage in the brain."
So do they theorize that these stressed neurons are expressing something at their surface to attract the notice of microglia?