Tc17 CD8+T cells accumulate in murine atherosclerotic lesions, but do not contribute to early atherosclerosis development

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Abstract

Aims: CD8+ T cells can differentiate into subpopulations that are characterized by a specific cytokine profile, such as the Tc17 population that produces interleukin-17. The role of this CD8+ T-cell subset in atherosclerosis remains elusive. In this study, we therefore investigated the contribution of Tc17 cells to the development of atherosclerosis. Methods and results: Flow cytometry analysis of atherosclerotic lesions from apolipoprotein E-deficient mice revealed a pronounced increase in RORγt+CD8+ T cells compared to the spleen, indicating a lesion-specific increase in Tc17 cells. To study whether and how the Tc17 subset affects atherosclerosis, we performed an adoptive transfer of Tc17 cells or undifferentiated Tc0 cells into CD8-/- low-density lipoprotein receptor-deficient mice fed a Western-type diet. Using flow cytometry, we showed that Tc17 cells retained a high level of interleukin-17A production in vivo. Moreover, Tc17 cells produced lower levels of interferon-γthan their Tc0 counterparts. Analysis of the aortic root revealed that the transfer of Tc17 cells did not increase atherosclerotic lesion size, in contrast to Tc0-treated mice. Conclusion: These findings demonstrate a lesion-localized increase in Tc17 cells in an atherosclerotic mouse model. Tc17 cells appeared to be non-atherogenic, in contrast to their Tc0 counterpart.

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Van Duijn, J., De Jong, M. J. M., Benne, N., Leboux, R. J. T., Van Ooijen, M. E., Kruit, N., … Slütter, B. (2021). Tc17 CD8+T cells accumulate in murine atherosclerotic lesions, but do not contribute to early atherosclerosis development. Cardiovascular Research, 117(14), 2755–2766. https://doi.org/10.1093/cvr/cvaa286

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