Back to Search
Start Over
TCR + CD4 - CD8 - (double negative) T cells protect from cisplatin-induced renal epithelial cell apoptosis and acute kidney injury.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2020 Jun 01; Vol. 318 (6), pp. F1500-F1512. Date of Electronic Publication: 2020 Apr 13. - Publication Year :
- 2020
-
Abstract
- Acute kidney injury (AKI) due to cisplatin is a significant problem that limits its use as an effective chemotherapeutic agent. T cell receptor <superscript>+</superscript> CD4 <superscript>-</superscript> CD8 <superscript>-</superscript> double negative (DN) T cells constitute the major T cell population in the human and mouse kidney, express programmed cell death protein (PD)-1, and protect from ischemic AKI. However, the pathophysiological roles of DN T cells in cisplatin-induced AKI is unknown. In this study, wild-type mice were treated with cisplatin (30 mg/kg) or vehicle, and the effects on kidney DN T cell numbers and function were measured. In vitro experiments evaluated effects of kidney DN T cells on cisplatin-induced apoptosis and PD ligand 1 (PD-L1) in renal epithelial cells. Adoptive transfer experiments assessed the therapeutic potential of DN T cells during cisplatin-induced AKI. Our results show that kidney DN T cell population increased at 24 h and declined by 72 h after cisplatin treatment. Cisplatin treatment increased kidney DN T cell proliferation, apoptosis, CD69, and IL-10 expression, whereas CD62L, CD44, IL-17A, interferon-γ, and TNF-α were downregulated. Cisplatin treatment decreased both PD-1 and natural killer 1.1 subsets of kidney DN T cells with a pronounced effect on the PD-1 subset. In vitro kidney DN T cell coculture decreased cisplatin-induced apoptosis in kidney proximal tubular epithelial cells, increased Bcl-2, and decreased cleaved caspase 3 expression. Cisplatin-induced expression of PD ligand 1 was reduced in proximal tubular epithelial cells cocultured with DN T cells. Adoptive transfer of DN T cells attenuated kidney dysfunction and structural damage from cisplatin-induced AKI. These results demonstrate that kidney DN T cells respond rapidly and play a protective role during cisplatin-induced AKI.
- Subjects :
- Acute Kidney Injury chemically induced
Acute Kidney Injury immunology
Acute Kidney Injury pathology
Animals
B7-H1 Antigen immunology
Cell Proliferation
Cells, Cultured
Coculture Techniques
Disease Models, Animal
Epithelial Cells pathology
Kidney Tubules, Proximal pathology
Male
Mice, Inbred C57BL
Phenotype
T-Lymphocyte Subsets immunology
Acute Kidney Injury prevention & control
Adoptive Transfer
Apoptosis
Cisplatin
Epithelial Cells immunology
Kidney Tubules, Proximal immunology
Receptors, Antigen, T-Cell immunology
T-Lymphocyte Subsets transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1466
- Volume :
- 318
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 32281417
- Full Text :
- https://doi.org/10.1152/ajprenal.00033.2020