Unconventional T cells and kidney disease

Unconventional T cells are a diverse and underappreciated group of relatively rare lymphocytes that are distinct from conventional CD4+ and CD8+ T cells, and that mainly recognize antigens in the absence of classical restriction through the major histocompatibility complex (MHC). These non-MHC-restricted T cells include mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells, γδ T cells and other, often poorly defined, subsets. Depending on the physiological context, unconventional T cells may assume either protective or pathogenic roles in a range of inflammatory and autoimmune responses in the kidney. Accordingly, experimental models and clinical studies have revealed that certain unconventional T cells are potential therapeutic targets, as well as prognostic and diagnostic biomarkers. The responsiveness of human Vγ9Vδ2 T cells and MAIT cells to many microbial pathogens, for example, has implications for early diagnosis, risk stratification and targeted treatment of peritoneal dialysis-related peritonitis. The expansion of non-Vγ9Vδ2 γδ T cells during cytomegalovirus infection and their contribution to viral clearance suggest that these cells can be harnessed for immune monitoring and adoptive immunotherapy in kidney transplant recipients. In addition, populations of NKT, MAIT or γδ T cells are involved in the immunopathology of IgA nephropathy and in models of glomerulonephritis, ischaemia–reperfusion injury and kidney transplantation. This Review examines the unique biological characteristics of unconventional T cells, including γδ T cells, mucosal-associated invariant T cells and natural killer T cells, and their roles in kidney injury, glomerulopathies and fibrosis. The authors also discuss the potential clinical applications of these cells, including in patients with kidney failure treated with dialysis or transplantation.