Activation and clonal expansion of CD8+T cells in patients with anti-NMDAR encephalitis revealed by single-cell RNA sequencing analysis

Abstract

AbstractBackgroundAnti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) is a rare and severe form of antibody-mediated autoimmune encephalitis. While the roles of B cells and NMDAR antibodies in NMDAR-E have been extensively studied, the contribution of T cell subsets to the development of the disease remains unclear.MethodsWe utilized single-cell RNA sequencing (scRNA-seq) and single-cell TCR sequencing (scTCR-seq) to examine a comprehensive collection of 45,088 individual immune cells sourced from both NMDAR-E patients and control subjects. Besides, we incorporated 14,536 immune cells obtained from a publicly available database. Additionally, cytometry analysis was conducted on samples from 60 NMDAR-E patients (with 89 samples) and 44 individuals in the control group. To investigate the influence of CD8+T cells on B cells, we performed in vitro co-culture experiments.ResultsWe observed the activation of effector memory CD8+T cells in the CSF and peripheral blood (PB) of NMDAR-E patients, accompanied by an expansion of TCR clones. These clonal CD8+T cells exhibited upregulated gene expression associated with cytotoxicity and cell trafficking. Furthermore, we detected elevated levels of KIR+CD8+T cells in the CSF and PB of NMDAR-E patients. Cell communication analysis revealed that these inhibitory KIR+CD8+T cells could interact with B cells through MHC-I molecules. Surprisingly, CD8+T cells isolated from the PB of NMDAR-E patients induced autologous B cell death, resulting in a higher rate of B cell apoptosis compared to the control group.ConclusionActivated CD8+T cells with TCR clones in NMDAR-E patients may contribute to the pathogenesis of NMDAR-E.