ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: PO0222

Selective Expansion of Kidney Double-Negative T Cells Is Driven by Renal Tubular Epithelial Cells Through Direct Cell-Contact and by Soluble Mediators

Session Information

  • AKI Mechanisms - 3
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Sadasivam, Mohanraj, Johns Hopkins University, Baltimore, Maryland, United States
  • Noel, Sanjeev, Johns Hopkins University, Baltimore, Maryland, United States
  • Gharaie, Sepideh, 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, Baltimore, Maryland, United States

Kidney TCRα/β+CD4-CD8-CD1d- double negative (DN) lymphocytes are a recently recognized unconventional T cell population with important roles in AKI and possibly other diseases like lupus. DN T cells expand after experimental AKI and exogenous delivery improves outcome. However, mechanisms underlying their regulation and expansion in the kidney are poorly understood. Here, we demonstrate a direct role for renal tubular epithelial cells (RTEC) in regulating homeostasis of kidney DN T cells.


Age-matched B6 WT, MHC I KO, MHC II KO and DKO (MHC I and II KO) mice were studied. T cell functional assays and an in-vitro co-culture system were used to investigate the functional relationship between RTEC and DN T cells. RTECs were isolated, purified and cultured in collagen-coated plates. Lymphocytes from both kidney and periphery were isolated, co-cultured with RTEC and analyzed by FACS.


DN T cells were anergic when cultured alone, even after stimulation with anti-CD3/CD28, but spontaneously proliferated when co-cultured with RTEC (DN; 1.2 ± 0.6% vs RTEC+DN; 13.8 ± 3.5%, p≤0.0001). Expansion was due to increased proliferation and decreased apoptosis of DN T cells. RTEC mediated expansion of DN T cells occurred by multiple mechanism including direct cell-contact and secretion of IL-7. Although activation of T cells required direct TCR crosslinking, activation of DN T cells was TCR-MHC independent as indicated by the ability of RTEC from mice lacking MHC class-I, class-II or DKO mice to induce proliferation of DN T cells (DN; 2.1 ± 0.8% vs RTEC (WT)+DN; 17.1 ± 1.5%, vs RTEC (MHC I KO)+DN; 21.2 ± 0.5%, vs RTEC (MHC II KO)+DN; 17.9 ± 1.8%, vs RTEC (DKO)+DN; 32.8 ± 0.3%, p≤0.0001). Reciprocally, DN T cells increased survival of RTEC as demonstrated using in-vitro assays. Our ongoing experiments are focusing on identifying surface molecules involved in mediating interactions between DN T cells and RTEC.


These results demonstrate a previously unknown functional relationship between RTEC and DN T cells that may explain the selective accumulation of DN T cells in the kidney and roles in normal and diseased kidney. The results have important implications for developing strategies to ameliorate AKI by promoting the survival of kidney DN T cells.


  • NIDDK Support