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

BackgroundAnti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) is a common and severe antibody-mediated autoimmune encephalitis. While the roles of B cells and NMDAR antibodies in NMDAR-E have been extensively studied, the involvement of T cell subpopulations in the disease progression remains unclear. MethodsThis study conducted single-cell RNA sequencing, single-cell TCR sequencing, and flow cytometry to analyze the T cell subpopulations and their transcriptomic characteristics in NMDAR-E patients and control individuals. Furthermore, it explored the interaction between CD8+T cells and B cells through in vitro cell co-culture and cell communication analysis. ResultsThe study found activated CD8+T cell subpopulations in the cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) of NMDAR-E patients, with some subpopulations exhibiting significant TCR clonal expansion. Differential expression gene analysis revealed upregulation of genes related to cytotoxicity, tissue residency, Th1, IFN, or TCR signaling in certain activated CD8+T cell and CD4+ memory T cell subpopulations. In vitro co-culture experiments demonstrated that CD8+T cells from the PBMCs of NMDAR-E patients could induce apoptosis of their own B cells. Cell interaction analysis revealed the existence of interactions between KIR+CD8+T cells and B cell subpopulations in NMDAR-E patients. ConclusionThis study explored the changes and transcriptomic characteristics of activated CD8+T cell subpopulations in the CSF and PBMCs of NMDAR-E patients. Additionally, it discovered the impact of CD8+T cells from NMDAR-E patients on their own B cells, providing new evidence for the interaction between CD8+T cells and B cells.