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Promotion of Demyelination by CD8 Follicular T Cells Expansion in Multiple Sclerosis

Zhang, JQ;Zhao, S;Jiang, D;Lu, J;Yang, S;Wang, J;


Multiple sclerosis (MS) has been considered to be a T cell-dependent autoimmune disease
of the central nervous system (CNS), so does the experimental autoimmune encephalomyelitis (EAE)
model. Recent studies identified CD8 follicular T cells (CD8+CXCR5+ T), a subset of CD8 T cells, in
antiviral, anti-tumor immunity and systemic autoimmunity, yet the role of CD8+CXCR5+ T cells in MS
and EAE remains unclarified.


CD8+CXCR5+ T cell frequency in peripheral blood of relapsing-remitting MS patients and
healthy controls were detected by flow cytometry and analyzed the correlation with disease activity. Flow
cytometry and multiplexed immunohistochemistry were performed to detect the dynamic changes and
locations of CD8+CXCR5+ T cells in secondary lymphoid organs (spleens and inguinal lymph nodes)
and CNS from EAE mice. RNA-seq, co-culture experiments and in vivo adoptive transfer were
performed to reveal the phenotypes and functions of CD8+CXCR5+ T cells.


Expansion of CD8+CXCR5+ T cells in both MS patients and EAE mice was detected during
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, infiltration of
CD8+CXCR5+ T cells, which were positively correlated with clinical score, were found in ectopic
lymphoid structures of spinal cords and germinal centers of spleens with helper cell-like and restricted
cytolytic phenotypes. In vitro co-culture experiments and CD8+CXCR5+ T -adoptive mice both
confirmed the potential cytotoxicity and the ability to provide B cell help of CD8+CXCR5+ T cells.


CD8+CXCR5+ T cells expanded and infiltrated in the CNS of MS patients and EAE mice
display multiple functions of CD8+ T cells and stronger pathogenic effect on demyelination.