Natural killer-like CD8+ T cells as a reservoir of clonal cells related to MS activity

Memory CD8+ T cells with natural killer-like properties are increased in MS patients and associated with disease activity. These cells belong to a reservoir of oligoclonal cells that infiltrate the CNS and exert cytotoxicity independent of T-cell receptor (TCR) involvement [1].

Although memory CD8+ T cells are more predominant than CD4+ T cells in MS lesions and drive autoimmune inflammation, they have not yet been identified. The current study set out to identify a cell involved in MS with a specific phenotypic and functional pattern in the periphery subtype.

Single-cell, high-dimensional profiling of peripheral memory CD8+ T cells was combined with TCRβ sequencing in a cohort of 17 MS patients and 11 healthy controls. An effector memory CD8+ T cell subtype could be identified that was increased in MS patients. Interestingly, this subtype was preferentially found during relapse episodes and belongs to a reservoir of peripheral oligoclonal cells. RNA sequencing confirmed the expression of natural killer-related molecules and their high cytotoxic potential. These natural killer-like CD8+CD94+ T cells were found to infiltrate the CNS. They were present in MS lesions, particularly in chronic active lesions. Functional assays showed that natural killer-like CD8+CD94+ T cells exert a cytotoxic function against the K562 cell line. Since this line is devoid of MHC molecules, the observed cytotoxicity is independent of TCR involvement.

1. Dugast E. High dimensional single-cell profiling identifies NK-like CD8+ T cells with high cytotoxic properties that are the reservoir of clonal cells related to disease activity in multiple sclerosis. OP133, ECTRIMS 2021 Virtual Congress, 13–15 October.

 

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Posted on 9 December 20219 December 2021