Identification and characteristics of a novel CD8αα T cell subset in a refractory myasthenia gravis patient

Abstract

Myasthenia gravis (MG) is an autoimmune disease that impairs neuromuscular transmission. Autoantibodies and cellular immunity mediate the immunopathology of MG, yet the mechanism of CD8⁺ T cells in this process remains elucidated. In this study, we discovered a novel subset of CD8αα⁺ T cells in the peripheral blood of an 18-year-old Chinese man diagnosed as MG, who has undergone thymectomy and persistent myasthenia crisis. Designated as CD161^neg T cell, this subset was characterized by TCRαβ⁺CD8αα⁺PLZF⁺Vα7.2⁺ but notably lacked CD161, distinct from mucosal-associated invariant T (MAIT) cells known for high CD161. The patient exhibited unusually high levels of CD161^neg T cells compared to other MG patients, which fluctuated with infections but not MG severity. RNA sequencing revealed that CD161^neg T cells lacked the genes characteristic of mature MAIT cells including CCR6, CXCR6, ZBTB16, and IL18RAP, but expressed cytotoxic T cell-related genes GZMH and IFNG. This study shed new light on the heterogeneity and complexity of CD8αα⁺ T cells in MG patients with thymoma.