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Abstract: SA-PO176

Analysis of TCRαβ+CD4+CD8+ (Double Positive) T Cells in Normal and Diseased Kidneys in Both Mice and Humans

Session Information

  • AKI: Mechanisms - III
    November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Noel, Sanjeev, Johns Hopkins University, Baltimore, Maryland, United States
  • Newman-Rivera, Andrea M., Johns Hopkins University, Baltimore, Maryland, United States
  • Patel, Shishir Kumar, Johns Hopkins University, Baltimore, Maryland, United States
  • Lee, Kyungho, Johns Hopkins University, Baltimore, Maryland, United States
  • Gharaie, Sepideh, Johns Hopkins University, Baltimore, Maryland, United States
  • Singla, Nirmish, Johns Hopkins University, Baltimore, Maryland, United States
  • Rabb, Hamid, Johns Hopkins University, Baltimore, Maryland, United States
Background

The roles of CD4, CD8 and double negative (DN) T cells are being increasingly recognized in normal and diseased kidneys. However, there is little information about kidney TCRαβ+CD4+CD8+ (double positive, DP) T cells. We therefore studied DPT cells in normal and diseased mouse and human kidneys.

Methods

Flow cytometry and single cell RNA-seq (scRNA-seq) were used to analyze kidney DPT cells in C57BL/6J mice at baseline, after ischemia reperfusion (IR) and cisplatin-induced AKI in comparison to CD4, CD8 and DN T cells. Effects of LCMV (virus) infection as well as gut microbiome were studied. Human kidneys from patients with renal cell carcinoma, with and without underlying ESRD were studied.

Results

DPT cells constituted a minor (0.16±0.03%) population of the total TCRαβ+ cells in normal mouse kidneys. AMNIS imaging flow cytometry confirmed the presence of both CD4 and CD8 co-receptors on individual DPT cells. DPT cells had significant Ki67 (87.4±3.3%) and PD1 (22.7±3.6%) expression. DPT cells had effector (69.6±7.5%) and central (18.3±3.5%) memory phenotype with significant IFNγ, TNFα and IL-17 expression. DPT cells expressed the metabolism-related proteins namely HKII, CPT1a and pS6. Percentage of DPT cells increased after ischemic AKI (0.47±0.11%, P=0.048) and cisplatin-induced AKI (0.40±0.14%, P=0.17) at 24 hrs compared to baseline. LCMV infection elevated kidney DPT cell percentage (0.40±0.08% vs 0.16±0.03%, P£0.01) and induced distinct functional and metabolic changes. Germ-free mice kidney DPT cell proportions and functional properties were comparable to WT mice. scRNA-seq analysis showed increased expression of Klf2 and Ccr7 and enrichment of TNFα and oxidative phosphorylation signaling related genes in DPT cells. Human kidneys contained high DPT cell populations in both adjacent normal (median (IQR) = 0.97(.44-1.49)%) and cancer portion of (median (IQR) = 9.69(0.29-10.40)%) renal cell carcinoma tissue.

Conclusion

TCRαβ+CD4+CD8+ double positive T cells constitute a minor population of both mouse and human kidney T cells, with distinct features in normal and diseased kidney compared to other T cells. Future studies of this T cell population are needed to evaluate their roles in normal and diseased kidney.

Funding

  • NIDDK Support