Autoimmune neurologic diseases
Numerous researches highlight the involvement of CD8+T cells in Multiple Sclerosis (MS) but the culprit CD8+T cells driving autoimmune inflammation have not been identified. We hypothesized that the cells able to provoke damages in the Central Nervous System (CNS), may have a specific phenotypic and functional pattern.
To identify this cell subtype, we analyze the single CD8+T cells molecular signatures by isolating single memory non MAIT CD8+T cells from the blood and the CSF of MS and Clinically Isolated Syndrome patients and from the blood of Healthy Controls and patients with other inflammatory neurological diseases. We then perform on each single-cells, qPCR of 96 genes involved in the CD8+T cell.
We thus are able to define subsets of CD8+T cells specific of MS by a set of genes including CCR7, CD62L, CD58, CD94, transcription factors (TBET and TCF7) and cytotoxic molecules (Granzyme A/B, perforin and granulysin) with unbiased analyses. Using T-SNE analysis, we identify a CD8+ effector memory T cell subtype with highly cytotoxic properties present only in MS patients. This MS cell subtype identification is confirmed by flow cytometry experiments on another cohort of patients. Interestingly, we also find that, in MS patients, the CSF CD8+T cells and those from the blood have a highly similar profile suggesting migration of the cells from the blood to the CNS.
Our data are the first to describe a specific cell subtype present only in MS patients made up of single cells strongly oriented toward an activated, effector and highly cytotoxic profile.