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

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2024-10, Vol.1870 (7), p.167303, Article 167303
• Main Authors: Ding, Jia-Qi, Zhang, Jun-Qi, Zhao, Si-Jia, Jiang, Dong-Bo, Lu, Jia-Rui, Yang, Shu-Ya, Wang, Jing, Sun, Yuan-Jie, Huang, Yi-Nan, Hu, Chen-Chen, Zhang, Xi-Yang, Zhang, Jia-Xing, Liu, Tian-Yue, Han, Chen-Ying, Qiao, Xu-Peng, Guo, Jun, Zhao, Cong, Yang, Kun
• Format: Article
• Language: English
• Subjects: Adult; Animals; Anti-MOG35–55 antibody; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; CD8+CXCR5+ T; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Demyelinating Diseases - immunology; Demyelinating Diseases - pathology; Disease Models, Animal; EAE; Ectopic lymphoid-like structures; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Female; Humans; Immunoglobulins - immunology; Immunoglobulins - metabolism; Male; Mice; Mice, Inbred C57BL; Middle Aged; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Receptors, CXCR5 - metabolism
• ISSN: 0925-4439; 1879-260X; 1879-260X
• DOI: 10.1016/j.bbadis.2024.167303

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-MOG35–55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses. [Display omitted] •Increased follicular CD8+ T cells in relapsing MS patients were positively correlated with new gadolinium-enhancement lesions in CNS.•Follicular CD8+ T cells in the ectopic lymphoid-like structures were involved in EAE progress.•Follicular CD8+ T cells may promote CNS demyelination through CD40L and IL-21 synergistically-mediated B cell activation and anti-MOG35–55 antibody production.