Role of follicular CD8+ T cells labeled with B cell helper immunotypes in multiple sclerosis and a murine model

Abstract

Background Multiple sclerosis (MS) has been considered to be a T cell-dependent autoimmune disease of the central nervous system (CNS), and so does the experimental autoimmune encephalomyelitis (EAE) model. Recent studies have revealed a specific subset of CD8 T cells, known as CD8 follicular T cells (CD8+CXCR5+ T), are involved in antiviral, anti-tumor immunity, and systemic autoimmunity. While the role of CD8+CXCR5+ T cells in MS and EAE remains unclear. Methods We detected CD8+CXCR5+ T cell frequency in the peripheral blood of relapsing-remitting MS patients and healthy controls by flow cytometry and analyzed its correlation with disease activity. To show the dynamic changes and locations of CD8+CXCR5+ T cells in secondary lymphoid organs and CNS from EAE mice, flow cytometry and multiplexed immunohistochemistry were performed. RNA-seq, co-culture experiments and in vivo adoptive transfer were then conducted to reveal the phenotypes and functions of CD8+CXCR5+ T cells. Results Expansion of CD8+CXCR5+ T cells in MS patients and EAE mice was detected during the acute phase. In relapsing MS patients, elevated frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions of CNS. In EAE mice, CD8+CXCR5+ T cells infiltrated in ectopic lymphoid structures of spinal cords and germinal centers of spleens were positively correlated with clinical score and highly expressed ICOS, CD40L, IL-21 and IL-6. In vitro co-culture experiments and CD8+CXCR5+ T-adoptive mice both confirmed the ability of CD8+CXCR5+ T cells to provide B cell help and contribute to disease progression. Conclusions CD8+CXCR5+ T cells which bridged cytotoxic T cells and B cells in MS might be a promising target for developing disease-modifying treatments in the future.