Abstract: FR-PO103
TCR+CD4-CD8- (Double-Negative) T Cells Protect from Cisplatin-Induced Renal Epithelial Cell Apoptosis and AKI
Session Information
- AKI: Mechanisms - Inflammation/Sepsis/Remote Injury
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Gong, Jing, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, JIANGSU , China
- Noel, Sanjeev, Johns Hopkins University , Baltimore, Maryland, United States
- Hsu, Joshua, Johns Hopkins Hospital, Baltimore, Maryland, United States
- Bush, Errol L., Johns Hopkins, Baltimore, Maryland, United States
- Arend, Lois J., Johns Hopkins Hospital, Baltimore, Maryland, United States
- Sadasivam, Mohanraj, Johns Hopkins University , Baltimore, Maryland, United States
- Lee, Sul A, Johns Hopkins University , Baltimore, Maryland, United States
- Kurzhagen, Johanna T., Johns Hopkins University , Baltimore, Maryland, United States
- Hamad, Abdel, Johns Hopkins University , Baltimore, Maryland, United States
- Rabb, Hamid, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
Background
Acute kidney injury (AKI) due to cisplatin is a significant problem that limits its use as an effective chemotherapeutic agent. TCR+CD4-CD8- (double negative - DN) T cells constitute a major T cell population in human and mouse kidney and protect from ischemic AKI. However the pathophysiologic roles of DN T cells in cisplatin-induced AKI is unknown
Methods
Mice were treated with cisplatin (30mg/kg) or vehicle and effect on kidney DN T cell numbers and function assessed using flow cytometry. In vitro studies evaluated effects of kidney DN T cells on cisplatin-induced apoptosis and PD ligand 1 (PD-L1) in renal epithelial cells. In vivo adoptive transfer studies assessed role of DN T cells on kidney structure and function during cisplatin-induced AKI
Results
Kidney DN T cell population increased (p<0.01) at 24 hours and declined (p<0.01) by 72 hours after cisplatin treatment. Cisplatin increased kidney DN T cell proliferation (p<0.05), apoptosis, CD69 (p<0.05) and IL10 (p<0.01) expression whereas CD62L (p=0.03), CD44, IL-17A, IFN-γ and TNF-α were (p<0.05) downregulated. Cisplatin decreased both kidney DN T cell PD1 (p<0.05) and NK1.1 (p<0.05) subsets with pronounced effect on PD1 subset. In vitro kidney DN T cells co-culture decreased cisplatin-induced apoptosis (p<0.05) in kidney proximal tubular epithelial cells (PTECs), increased expression of Bcl-2 (p<0.05) decreased cleaved caspase 3 (p<0.05), and attenuated PTEC PD-L1 expression (p<0.05). Adoptive transfer of DN T cells attenuated kidney dysfunction (p<0.05) and structural damage (p<0.05) from cisplatin-induced AKI
Conclusion
These results demonstrate that kidney DN T cells respond rapidly and play a protective role during cisplatin-induced AKI. DN T cells may have important translational implications for humans undergoing cisplatin and immune checkpoint inhibitor therapy for cancer
Funding
- NIDDK Support