scRNAseq of CD8+ T cells from autoimmune encephalitis

Single-cell RNA sequencing in seven anti-Ri autoimmune encephalitis (AIE) patients and three controls showed that neuron-reactive CD8+ T cells are cytotoxic KIR+ CD8+ regulatory T cells. In Ri-AIE, these cells had reduced KIR and IKZF2 (Helios) expression, alongside activated TCR signaling and elevated TNF and IFNG. They also overexpressed TOX, linked to brain-infiltrating cytotoxicity. These findings suggest a loss of regulatory function in KIR+ CD8+ T cells contributes to Ri-AIE pathogenesis. Ex vivo human CD8+ T cells from 11 different samples were isolated from total PBMCs by Magnetic-associated cell sorting (MACS). 8 of these samples originated from patients with Ri AIE (7 samples from patients at time of disease and 1 at remission). 3 of these samples were taken from age-matched donors with non-autoimmune neurological disorders.