TCR+CD4-CD8-(double negative) T cells protect from cisplatin-induced renal epithelial cell apoptosis and acute kidney injury

Jing Gong, Sanjeev Noel, Joshua Hsu, Errol L. Bush, Lois J. Arend, Mohanraj Sadasivam, Sul A. Lee, Johanna T. Kurzhagen, Abdel Rahim A. Hamad, Hamid Rabb

Research output: Contribution to journalArticlepeer-review


Acute kidney injury (AKI) due to cisplatin is a significant problem that limits its use as an effective chemotherapeutic agent. T cell receptor+CD4-CD8-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 cisplatininduced 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 cisplatininduced apoptosis in kidney proximal tubular epithelial cells, increased Bcl-2, and decreased cleaved caspase 3 expression. Cisplatininduced 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 cisplatininduced AKI.

Original languageEnglish (US)
Pages (from-to)F1500-F1512
JournalAmerican Journal of Physiology - Renal Physiology
Issue number6
StatePublished - Jun 2020


  • Acute kidney injury
  • Cisplatin
  • Double negative T cells
  • Kidney epithelial cells
  • T cell receptor

ASJC Scopus subject areas

  • Physiology
  • Urology


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