A CD57+ cytotoxic CD8 T cell subset associated with fibrotic lung disease in systemic sclerosis

Sasaki, T.; Cao, Y.; Marks, K.; Higashioka, K.; Elahee, M.; Ainsworth, R.; Taylor, K.; Bottini, N.; Wolters, P.; Kamiya, M.; Kim, E. Y.; Boin, F.; Rao, D. A.

doi:10.1101/2025.01.27.635121

bioRxiv · 10.1101/2025.01.27.635121

A CD57+ cytotoxic CD8 T cell subset associated with fibrotic lung disease in systemic sclerosis

Sasaki, T.·Cao, Y.·Marks, K.·Higashioka, K.·Elahee, M.·Ainsworth, R.·Taylor, K.·Bottini, N.·Wolters, P.·Kamiya, M.·Kim, E. Y.·Boin, F.·Rao, D. A.

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Abstract

Interstitial lung disease (ILD) is a major cause of morbidity and mortality in systemic sclerosis (SSc); however, the immunopathologic mechanisms driving lung disease in SSc are unclear. T cells have been implicated as a likely driver of lung injury in SSc. Here, we have evaluated T cells in blood and lungs of patients with SSc-ILD and identified a specific population of cytotoxic CD8 T cells that is expanded in SSc-ILD patients. Cytotoxic effector memory CD8 T cells marked by CD57 expression are preferentially expanded in SSc-ILD patients compared to SSc patients without ILD and controls and show prominent clonal expansion. These CD57+ T effector memory (TEM) cells differ from T effector memory cells re-expressing CD45RA (TEMRA) transcriptomically and functionally, with cytotoxic function that is enhanced by CD155 engagement of the costimulatory receptor CD226. Analyses of cells from ILD lungs indicate endothelial cells as a likely source of CD155 to activate CD57+ cytotoxic T cells. Together, the results implicate a CD57+ cytotoxic CD8 T cell population as a potential mediator of lung injury in SSc-ILD.

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Sasaki, T., Cao, Y., Marks, K., Higashioka, K., Elahee, M., Ainsworth, R., Taylor, K., Bottini, N., Wolters, P., Kamiya, M., Kim, E. Y., Boin, F., Rao, D. A.. 2025-01-29. A CD57+ cytotoxic CD8 T cell subset associated with fibrotic lung disease in systemic sclerosis. https://doi.org/10.1101/2025.01.27.635121

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