Kidney resident-memory CD8+ T cells drive chronic high blood pressure 9288

Description High blood pressure, a chronic disease impacting half of American adults, is a major cause of cardiovascular mortality. T cells play a critical role in the pathogenesis of hypertension. Our studies indicate activated CD8? T cells (CD8Ts) disrupt kidney function and promote salt retention, thereby exacerbating hypertension. We show that ATP aberrantly activates CD8Ts via the P2X7 receptor, facilitating their infiltration into the kidney. Notably, CD8Ts persist in the kidneys despite antihypertensive treatment, implying the formation of a resident memory (CD8Trm) population that may drive persistent and recurrent hypertension. Building on this, we observed a significant expansion of renal CD8Trms in the classic DOCA-salt-induced chronic hypertension model in wild-type (WT) mice. In contrast, T cell-specific TGFβ receptor knockout (Tsp-TGFβR-KO) mice, which cannot establish Trm cells, exhibited significantly lower blood pressure in this model. To assess hypertension recurrence, both Trm-deficient Tsp-TGFβR-KO and WT mice were subjected to Ang II infusion, followed by a week of normalization before rechallenging with high salt diet. Only WT mice with renal Trm developed recurrent hypertension, whereas Tsp-TGFβR-KO mice were protected from recurrent hypertension. Additionally, renal Trm cells expressed higher levels of P2X7 than non-memory CD8Ts. These findings identify renal CD8Trm as a novel and critical therapeutic target to limit the progression and recurrence of hypertension. Funding Sources NIH F31HL175932 (Deck) AHA 24PRE1198737 (Deck) NIH T32 T-SPaT GM150536 (Deck) NIH R01-HL146713 (Mu) AHA 23TPA1076467(Mu)