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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)