Key Points
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CD8+ T-cell homeostasis is altered in the peripheral blood of patients with autoimmune arthritis
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The close association of MHC class I polymorphisms with disease risk and the correlation of CD8+ T-cell number with disease outcome support the idea that this cell population has a role in autoimmune arthritis
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At sites of chronic inflammation, the phenotype of CD8+ T cells is heterogeneous and includes proinflammatory and anti-inflammatory features
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In inflammatory environments, CD8+ T cells lose susceptibility to regulation, and this loss is sustained by autocrine release of proinflammatory cytokines
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Subsets of memory CD8+ T cells upregulate negative costimulatory markers and either develop an exhausted phenotype or display a tissue-instructed differentiation, as in tissue-resident memory T cells
Abstract
CD8+ T cells are key players in the body's defence against viral infections and cancer. To date, data on the role of CD8+ T cells in autoimmune diseases have been scarce, especially when compared with the wealth of research on CD4+ T cells. However, growing evidence suggests that CD8+ T-cell homeostasis is impaired in human autoimmune diseases. The contribution of CD8+ T cells to autoimmune arthritis is indicated by the close association of MHC class I polymorphisms with disease risk, as well as the correlation between CD8+ T-cell phenotype and disease outcome. The heterogeneous phenotype, resistance to regulation and impaired regulatory function of CD8+ T cells — especially at the target organ — might contribute to the persistence of autoimmune inflammation. Moreover, newly identified populations of tissue-resident CD8+ T cells and their interaction with antigen-presenting cells might have a key role in disease pathology. In this Review, we assess the link between CD8+ T cells, autoimmune arthritis and the basis of their homeostatic changes under inflammatory conditions. Improved insight into CD8+ T cell-specific pathogenicity will be essential for a better understanding of autoimmune arthritis and the identification of new therapeutic targets.
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Acknowledgements
A.P. is supported by the European Union Seventh Framework Programme (501100004963, 289903). F.V.W. is supported by the VIDI grant from the Netherlands Organization for Scientific Research (NWO, ZonMW) and by the Dutch Arthritis Foundation Reumafonds
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A.P. researched data for the article and wrote the manuscript. F.V.W. reviewed and edited the manuscript before submission. A.P. and F.V.W. contributed equally to discussions of the content.
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Petrelli, A., van Wijk, F. CD8+ T cells in human autoimmune arthritis: the unusual suspects. Nat Rev Rheumatol 12, 421–428 (2016). https://doi.org/10.1038/nrrheum.2016.74
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DOI: https://doi.org/10.1038/nrrheum.2016.74
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