Myasthenia gravis (MG) is a chronic autoimmune disease mediated by T cells. While previous studies have predominately focused on CD4 T cells in MG pathogen, our research seeks to examine the uncertain role of CD8 T cells.

Multi-color flow cytometry was performed on CD8 T cells among MG patients (N=42) with no immunosuppressant (No-IS), those treated with steroids and healthy controls (HC) (N=20). IsoPlexis single-cell platform was applied to a subset of patients to detect cytokine production prior to and post steroid treatment (N=12). NanoString RNA sequencing of 752 autoimmune related genes was performed on CD8 T cells to validate the cytokine changes (N=26).

Memory (CD27+) and Exhausted (CTLA4+, PD-1+, EMOES+) CD8 T cell were increased in No-IS MG patients. In unbiased Self-Organizing Maps (FlowSOM), central memory and CXCR5+ CD8 T cells were increased in No-IS compared to HC and decreased post treatment. Single-cell analysis detected elevated frequencies of effector and inflammatory cytokines, including granzyme B, IFN-g, IL-9, MIP-1b, TNF-a, IL-17A, GM-CSF, IL-12, and MIP-1a in the No-IS group. Effector and inflammatory cytokines and frequencies of polyfunctional CD8 T cells significantly decreased with steroids treatment. RNA sequencing assays are in process and results will be presented at the conference.

Analysis of CD8 T cells demonstrates an effector phenotype with prominent polyfunctional inflammatory cytokine function in MG patients. Steroid treatment reduces the CD8 T cell proinflammatory phenotype. This data suggests CD8 T cells contribute to MG pathogenesis and may potentially serve as a biomarker for monitoring response to treatment.