Kidney double positive T cells have distinct characteristics in normal and diseased kidneys

• Published in: Scientific reports Vol. 14; no. 1; p. 4469
• Main Authors: Noel, Sanjeev, Newman-Rivera, Andrea, Lee, Kyungho, Gharaie, Sepideh, Patel, Shishir, Singla, Nirmish, Rabb, Hamid
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23-02-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/1619; 692/4022; 692/4022/1585; AKI; Animals; CD4 antigen; CD8 antigen; Cisplatin; Cisplatin - pharmacology; Double positive T cells; DPT cells; Humanities and Social Sciences; Humans; Inflammation; Intestinal microflora; Ischemia; Ischemia - pathology; Ischemia reperfusion; Kidney - metabolism; Kidneys; Krueppel-like factor; Lymphocytes; Lymphocytes T; Metabolism; Mice; multidisciplinary; Oxidative phosphorylation; PD-1 protein; Phenotypes; Phosphorylation; Renal cell carcinoma; Reperfusion; Science; Science (multidisciplinary); T-Lymphocytes - metabolism; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Viral infections; Virus Diseases - pathology; γ-Interferon; Double positive T cells; DPT cells; Ischemia reperfusion; Cisplatin; AKI
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-54956-3

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.