| 研究実績の概要 |
The autoimmune disease multiple sclerosis (MS) can transition from a relapsing-remitting form (RRMS) into a chronic progressive form (secondary progressive MS, SPMS). SPMS pathogenesis remains poorly understood with diagnosis based entirely on retrospective clinical monitoring. We have studied the role of Eomes-expressing CD4+ T cells (Eomes+ Th cells), Th cell subset previously identified as pathogenic in a mouse model of late/chronic autoimmune CNS inflammation.
As part of Objective 1, we have examined the surface and intracellular phenotype of Eomes-expressing Th cells using flow cytometry. Using a target-scanning approach to this cytometry, we have identified a number of surface molecules associated with cytotoxic function that are potentially linked to function of these cells. Moreover, these molecules have allowed flow cytometric cell sorting of different potential subsets of Eomes+ Th cells for ongoing analysis by Nanostring. Such peripheral cells, as well as those we have sorted from the CNS of SPMS autopsy samples have been characterised by TcR repertoire sequencing and indicate oligoclonal expansion.
For objective 2, we reported the association of cytotoxic Eomes+ CD4+ Th cells with active disease in SPMS (Raveney et al., 2021). As an extension to this, we have continued to follow up patients from our cohort, to monitor Eomes+ Th cells over time with disease activity. Furthermore, we have examined these cells in a new cohort of patients that are undergoing treatment from a newly approved drug for SPMS, Siponimod, that may target CNS T cells.
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