Unconventional T cells and kidney disease

• Published in: Nature reviews. Nephrology Vol. 17; no. 12; pp. 795 - 813
• Main Authors: Kaminski, Hannah, Couzi, Lionel, Eberl, Matthias
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-12-2021; Nature Publishing Group
• Subjects: 631/250/1619/554; 692/308/1426; 692/4022/1585/104/1586; 692/4022/1950/1724; Antigens; Biomarkers; CD8-Positive T-Lymphocytes; Cytomegalovirus; Cytotoxicity; Humans; Immune system; Immunology; Immunotherapy; Infections; Kidney Diseases; Kidney transplants; Life Sciences; Lymphocytes; Medicine; Medicine & Public Health; Mucosal-Associated Invariant T Cells; Natural Killer T-Cells; Nephrology; Peptides; Peritoneal dialysis; Review Article; T cell receptors
• ISSN: 1759-5061; 1759-507X; 1759-507X
• DOI: 10.1038/s41581-021-00466-8

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.
Key points
Unconventional T cells, such as γδ T cells, mucosal-associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cells, are distinct from classical CD4
+
and CD8
+
T cells and can have either protective or pathogenic roles in a range of inflammatory and autoimmune conditions related to acute and chronic kidney disease.
Vγ9Vδ2 T cells and MAIT cells respond to metabolites shared by a wide range of microbial pathogens, which may have implications for early diagnosis, risk stratification and targeted treatment of peritoneal dialysis-related peritonitis.
Non-Vγ9Vδ2 γδ T cells expand during cytomegalovirus (CMV) infection in kidney transplant recipients and contribute to viral clearance, which suggests that they can be harnessed for immune monitoring and for adoptive immunotherapy in refractory CMV infections.
IgA nephropathy is accompanied by oligoclonal expansion of γδ T cells in blood and the kidneys; this expansion correlates with disease progression and may contribute to immunopathology.
In murine models of glomerulonephritis, kidney γδ T cells are an important source of IL-17A, which is necessary for the recruitment of macrophages, neutrophils and T cells, and contributes to the development of kidney fibrosis.
Murine type I and type II NKT cells have opposite roles in ischaemia–reperfusion injury and may be relevant for allograft tolerance, as well as kidney protection in lupus nephritis or crescentic glomerulonephritis.