CD8⁺ T cells in human autoimmune arthritis: The unusual suspects

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.