TCRαβ+ CD4−/CD8– “double negative” T cells in health and disease—implications for the kidney

Double negative (DN) T cells, one of the least studied T lymphocyte subgroups, express T cell receptor αβ but lack CD4 and CD8 coreceptors. DN T cells are found in multiple organs including kidney, lung, heart, gastrointestinal tract, liver, genital tract, and central nervous system. DN T cells suppress inflammatory responses in different disease models including experimental acute kidney injury, and significant evidence supports an important role in the pathogenesis of systemic lupus erythematosus. However, little is known about these cells in other kidney diseases. Therefore, it is important to better understand different functions of DN T cells and their signaling pathways as promising therapeutic targets, particularly with the increasing application of T cell–directed therapy in humans. In this review, we aim to summarize studies performed on DN T cells in normal and diseased organs in the setting of different disease models with a focus on kidney.