| First Author | Sadasivam M | Year | 2019 |
| Journal | J Am Soc Nephrol | Volume | 30 |
| Issue | 2 | Pages | 277-292 |
| PubMed ID | 30622155 | Mgi Jnum | J:293072 |
| Mgi Id | MGI:6435839 | Doi | 10.1681/ASN.2018080815 |
| Citation | Sadasivam M, et al. (2019) Activation and Proliferation of PD-1(+) Kidney Double-Negative T Cells Is Dependent on Nonclassical MHC Proteins and IL-2. J Am Soc Nephrol 30(2):277-292 |
| abstractText | BACKGROUND: CD4(-) CD8(-) double-negative (DN) alphabeta T cells with innate-like properties represent a significant component of T cells in human and mouse kidneys. They spontaneously proliferate in the steady state and protect against ischemic AKI. However, the mechanisms regulating DN T cell homeostasis and responses to external danger signals from "sterile" inflammation remain poorly understood. METHODS: We used knockout mice, functional assays, and an established ischemic AKI model to investigate the role of various MHC class I and II molecules in regulating kidney DN T cells. We also studied human nephrectomy samples. RESULTS: Deficiency of beta2m-dependent MHC class I (but not MHC class II) molecules led to significant reduction in frequency or absolute numbers of kidney DN T cells due to impaired activation, proliferation, increased apoptosis, and loss of an NK1.1(+) subset of DN T cells. The remaining DN T cells in beta2m knockout mice mainly comprised a programmed cell death protein-1 receptor (PD-1(+)) subset that depends on IL-2 provided by conventional T cells for optimal homeostasis. However, this PD-1(+) subset remained highly responsive to changes in milieu, demonstrated by responses to infused lymphocytes. It was also the major responder to ischemic AKI; the NK1.1(+) subset and CD8(+) T cells had minimal responses. We found both DN T cell subsets in normal and cancerous human kidneys, indicating possible clinical relevance. CONCLUSIONS: DN T cells, a unique population of kidney T cells, depend on nonclassical beta2m molecules for homeostasis and use MHC-independent mechanisms to respond to external stimuli. These results have important implications for understanding the role these cells play during AKI and other immune cell-mediated kidney diseases. |
