Resident Memory-like CD8⁺ T Cells Are Involved in Chronic Inflammatory and Neurodegenerative Diseases in the CNS

Resident memory T (Trm) cells are a unique population that can survive and function in a compartmentalized tissue with inflammatory potential. We aim to investigate the alteration of Trm population in acute/chronic inflammatory and neurodegenerative diseases in the CNS.

The frequencies of CD4⁺ and CD8⁺ T cells expressing both CD69 and CD103, the markers for Trm cells, were quantified in the peripheral blood and CSF (n = 80 and 44, respectively) in a cross-sectional manner. The transcriptional profile of Trm-like population in the CSF was further analyzed using a public single-cell dataset.

The frequency of CD69⁺CD103⁺CD8⁺ T cells was strikingly higher in the CSF than in the peripheral blood (among memory fraction, 13.5% vs 0.11%, difference (mean [SE]): 13.4% [2.9]). This CD69⁺CD103⁺CD8⁺ T-cell population was increased in the CSF from patients with chronic inflammatory diseases including multiple sclerosis and with neurodegenerative diseases such as Parkinson disease and Alzheimer disease compared with controls (11.5%, 13.0%, 8.1% vs 2.9%, respectively). By contrast, the frequency was not altered in acute inflammatory conditions in the CNS (4.0%). Single-cell RNAseq analysis confirmed Trm signature in CD69⁺CD103⁺CD8⁺ T cells in the CSF, supporting their Trm-like phenotype, which was not clear in controls.

Collectively, an increase in CD69⁺CD103⁺CD8⁺ Trm-like population in the CSF is related with both chronic neuroinflammatory and some neurodegenerative diseases in the CNS, suggesting a partially shared pathology in these diseases.