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Updated: May 29, 2025
Isolation of Double Negative αβ T Cells from the Kidney
Published on: May 16, 2014
Renal Tubular Epithelial Cell-Derived IL-7 Drives Expansion and Protective Effects of Double-Negative T Cells in
Mohanraj Sadasivam1,2, Sanjeev Noel3, Kyungho Lee3
1Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Background:
Previous studies have demonstrated that double-negative (DN) αβ T cells play an important role in immune responses during ischemic acute kidney injury (AKI). Here, we investigate the role of γ-chain cytokines in driving DN T cell proliferation in steady state and AKI, focusing on IL-2, IL-7, and IL-15.
Methods:
We assessed DN T cell proliferation in vitro in response to IL-2, IL-7, and IL-15, with co-culture experiments using renal tubular epithelial cells (RTECs) and IL-7 blockade. In vivo, wild-type and IL-7r knockout mice were studied to evaluate the impact of IL-7 on DN T cell expansion and kidney function during AKI. Human RTECs confirmed the relevance of these findings.
Results:
All three cytokines promoted DN T cell proliferation in vitro, with IL-7 inducing the most robust expansion. Co-culture experiments showed RTECs as a key IL-7 source, and blockade reduced DN T cell expansion. In vivo, IL-7 complexes administered to wild-type mice increased DN T cells and selectively expanded the PD-1+ subset. IL-7 deficiency worsened renal outcomes during AKI. Human RTECs activated peripheral human DN T cells in vitro.
Conclusion:
These results establish IL-7 as pivotal for DN T cell expansion and highlight RTECs' role in DN T cell homeostasis.
