Follicular CD8⁺ T cells promote immunoglobulin production and demyelination in multiple sclerosis and a murine model

Emerging evidence underscores the importance of CD8⁺ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8⁺ T cells (CD8⁺CXCR5⁺ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8⁺CXCR5⁺ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8⁺CXCR5⁺ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8⁺CXCR5⁺ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8⁺CXCR5⁺ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8⁺CXCR5⁺ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG_35-55 antibodies and contribute to the disease progression. Consequently, CD8⁺CXCR5⁺ T cells may play a role in CNS demyelination through heightening humoral immune responses.