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Updated: Jul 2, 2025

Isolation of Double Negative αβ T Cells from the Kidney
Published on: May 16, 2014
Kidney double positive T cells have distinct characteristics in normal and diseased kidneys
Sanjeev Noel1, Andrea Newman-Rivera2, Kyungho Lee2
1Department of Medicine, Johns Hopkins University, Ross 970, 720 Rutland Avenue, Baltimore, MD, 21205, USA. snoel6@jhmi.edu.
Abstract:
Multiple types of T cells have been described and assigned pathophysiologic functions in the kidneys. However, the existence and functions of TCR+CD4+CD8+ (double positive; DP) T cells are understudied in normal and diseased murine and human kidneys. We studied kidney DPT cells in mice at baseline and after ischemia reperfusion (IR) and cisplatin injury. Additionally, effects of viral infection and gut microbiota were studied. Human kidneys from patients with renal cell carcinoma were evaluated. Our results demonstrate that DPT cells expressing CD4 and CD8 co-receptors constitute a minor T cell population in mouse kidneys. DPT cells had significant Ki67 and PD1 expression, effector/central memory phenotype, proinflammatory cytokine (IFNγ, TNFα and IL-17) and metabolic marker (GLUT1, HKII, CPT1a and pS6) expression at baseline. IR, cisplatin and viral infection elevated DPT cell proportions, and induced distinct functional and metabolic changes. scRNA-seq analysis showed increased expression of Klf2 and Ccr7 and enrichment of TNFα and oxidative phosphorylation related genes in DPT cells. DPT cells constituted a minor population in both normal and cancer portion of human kidneys. In conclusion, DPT cells constitute a small population of mouse and human kidney T cells with distinct inflammatory and metabolic profile at baseline and following kidney injury.
Insights
Double positive (DP) T cells are a minor population in mouse and human kidneys. These kidney DP T cells exhibit inflammatory and metabolic functions, changing with injury.
Area of Science:
- Immunology
- Nephrology
- Cell Biology
Background:
- Kidney T cell populations are crucial for renal pathophysiology.
- The role of TCR+CD4+CD8+ (double positive; DP) T cells in kidney health and disease remains understudied.
Purpose of the Study:
- To investigate the presence, phenotype, and function of kidney DP T cells in mice and humans.
- To determine how kidney DP T cells respond to injury and other stimuli.
Main Methods:
- Flow cytometry and scRNA-seq analysis of kidney cells from mice and human renal cell carcinoma patients.
- Assessment of DP T cells at baseline and following ischemia-reperfusion (IR), cisplatin injury, and viral infection.
Main Results:
- DP T cells are a minor population in mouse and human kidneys, expressing markers of inflammation, memory phenotype, and metabolic activity (e.g., IFNγ, TNFα, IL-17, GLUT1).
- Kidney injury (IR, cisplatin, viral infection) increased DP T cell proportions and altered their functional and metabolic profiles.
- scRNA-seq revealed increased expression of Klf2, Ccr7, and enrichment of TNFα and oxidative phosphorylation pathways in DP T cells post-injury.
Conclusions:
- Kidney DP T cells represent a distinct T cell subset with significant inflammatory and metabolic characteristics.
- DP T cells dynamically respond to kidney injury, suggesting a role in renal pathophysiology.
- Further research into kidney DP T cells could reveal novel therapeutic targets for kidney diseases.
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