Key result
T cell TGFβ receptor knockout mice lacking renal CD8Trm cells resist chronic and recurrent hypertension.
Why the study?
Although T cells contribute to hypertension, the mechanisms by which they sustain hypertensive pathology remain unclear.
Renal CD8Trm cells sustain hypertension through ATP and TGFβ-driven activation, providing a potential immunological target to prevent hypertension recurrence.
Introduction T cells critically contribute to hypertension, a condition affecting nearly half of American adults and driving cardiovascular mortality. However, the mechanisms by which these cells sustain hypertensive pathology remain unclear. We identified a persistent, memory-like CD8T cell population in the kidneys of hypertensive humans and hypothesize that kidney-resident memory CD8T cells (CD8Trm) establish a renal salt-retention memory that drives the chronic progression and recurrence of hypertension. Methods Kidneys from hypertensive patients and mice were analyzed. Trm-deficient mice (T cell-specific TGFβ receptor knockout; Tsp-TGFβR-KO) were used to assess the role of Trms in hypertension. Flow cytometry, single-cell metabolic profiling, and histopathology characterized renal immune populations. Mechanistic studies employed Rag2OT-I mice and ex vivo stimulation of CD8 T cells with ATP + TGFβ to test antigen-independent Trm formation and effects on distal nephron epithelial cells. Results Abundant renal CD8Trm were identified in both hypertensive patients and mice. In contrast, Tsp-TGFβR-KO mice showed blunted blood pressure in response to chronic hypertensive stimuli. In the salt-memory model, Tsp-TGFβR-KO mice developed initial hypertension but were protected from recurrence upon high-salt rechallenge, confirming Trm involvement in renal salt-retention memory. Renal CD8Trm formation occurred without antigen; Rag2OT-I mice without OVA exposure still generated P2X7+ CD8Trm, implicating ATP-driven CD8T-activation. Ex vivo ATP plus TGFβ treatment induced Trm formation with canonical markers, cytokine production, and distinct metabolic profiles. Co-culture with renal tubule cells enhanced sodium retention, linking immune activation to renal salt handling. Conclusion We identify a renal CD8Trm population that sustains hypertension through ATP+TGFβ-driven activation. This CD8Trm-salt axis anchors immune-hypertensive memory, offering a new immunological target to prevent hypertension recurrence.
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Deck et al. (2026) studied Hypertension. T cell-specific TGFβ receptor knockout (Tsp-TGFβR-KO) vs. Control mice was evaluated on Blood pressure response to chronic hypertensive stimuli and hypertension recurrence. T cell-specific TGFβ receptor knockout mice lacking renal CD8Trm cells showed blunted blood pressure responses to chronic hypertensive stimuli and were protected from hypertension recurrence.
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