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.

Scientific Reports
|February 23, 2024
PubMed

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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