Kidney Week

Abstract: TH-PO0286

Kidney Memory for Salt Sensitivity Resides in T Cells Driving Chronic Hypertension

Session Information

• Hypertension and CVD: Mechanisms
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1601 Hypertension and CVD: Basic

Authors

• Deck, Katherine S., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Katherine S. Deck

• Liu, Yunmeng, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Yunmeng Liu, PhD

• Mora, Christoph J., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Christoph J. Mora

• Rogers, Pamela, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Pamela Rogers, MS

• Deng, Shuoqiu, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Shuoqiu Deng, MS

• Rafferty, Tonya M., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Tonya M. Rafferty

• Mu, Shengyu, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

Shengyu Mu, MBBS, PhD

Background

Kidneys carry a memory for salt-sensitivity that drives chronic hypertension and its frequent relapse. Yet the cell type behind this pathogenic imprint remains unknown. We recently observed a long-lived renal CD8+ T cell (CD8T) population in hypertensive humans and mice, leading us to propose that kidney resident memory CD8Ts (CD8Trm) encode the memory of salt-sensitivity, driving the chronic progression and recurrence of hypertension.

Methods

First, our immunofluorescent staining of human kidney revealed the clinical manifestation of a Trm population and was confirmed by multiple mouse hypertension models, including the classic DOCA-salt model. Its novel memory model counterparts, SNA+Ch (Salt, uniNephrectomy, Aldosterone + Challenge) and Angiotensin II (Ang II)-induced salt memory, evaluated the recurrence of salt-sensitive hypertension via a 1% high salt water challenge. Then, a T-cell-specific TGFβRII KO (Tsp-TGFβR KO), with impaired Trm formation, scrutinized the requirement for Trm on the development and recurrence of salt-sensitive hypertension. Biotelemetry measured blood pressure, with the kidneys, blood, and spleen analyzed via flow cytometry and immunofluorescent staining.

Results

Here, we identified a significant Trm population within hypertensive human kidney biopsies. In mice, significant expansion of kidney CD8Trms occurred with the development of hypertension and persisted with its recurrence. During aldosterone-based salt-sensitive hypertension, we observed that the Trm-deficient mTsp-TGFβR KO mice had significantly attenuated blood pressure. However, both the Trm-deficient Tsp-TGFβR KO and WT reached similar degrees of hypertension during initial Ang II administration, with greater levels of activated, central and effector memory CD8Ts systemically and overall greater renal CD8T infiltration in the Tsp-TGFβR KO mice. Despite this, the Tsp-TGFβR KO mice experienced protection against the recurrence of hypertension with the inability of infiltrated CD8Ts to develop into a Trm population. Throughout all of the memory models, we did not note kidney injury in H&E staining or KIM-1 and NGAL western blots.

Conclusion

In summary, we identified that a renal resident memory CD8T population had developed within the kidney during hypertension, engraving the chronic progression and recurrence of salt-sensitivity.

Funding

• Other NIH Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025y467bvn4