O14 KIDNEY RESIDENT MEMORY T CELLS MEDIATE THE CHRONIC PROGRESSION OF HYPERTENSION

Abstract

A significant challenge in treating hypertension is insufficient blood pressure (BP) control and its recurrence. Previously, we described the contribution of CD8 T cells (CD8Ts) to the pathogenesis of salt-sensitive hypertension. Notably, despite antihypertensive therapy temporarily lowering BP in hypertensive mice, the T cell residency was not disrupted within the kidneys, and hypertension recurred when treatment was ceased. We hypothesize that the CD8Ts established a long-living resident memory (Trm) population in the kidney that instigates the recurrence of hypertension. To examine this, we utilized both wild-type (WT) and T-cell-specific KO of TGFβRII (Tsp-TGFβRKO) mice, which prevents the formation of Trms. Blood pressure was recorded continuously with radiotelemetry. Hypertension was induced with the classic DOCA-salt model and an Angiotensin II (Ang II)-induced salt memory model to mimic the clinical recurrence of hypertension with high salt intake. In this salt-memory model, a one-week infusion of Ang II paired with high salt-induced hypertension before being allowed to return to normal blood pressure. A chronic high salt intake challenge then tested the recurrence of hypertension. Both splenic and renal T cell populations were characterized using flow cytometry. As expected, DOCA-salt treatment led to salt-sensitive hypertension in WT mice along with the development of a significant CD8Trm population within their kidneys. These CD8Trms were notably diminished in the kidneys of DOCA-treated Tsp-TGFβRKO mice who also had attenuated blood pressure elevation. While testing the recurrence of hypertension during the Ang II-induced salt-memory model both WT and Tsp-TGFβKO reached the same degree of hypertension during Ang II-salt and baseline blood pressure before and after Ang II-salt. However, only the WT developed Trm and had the recurrence of hypertension with high salt challenge whereas both were lost in the Tsp-TGFβKO mice. In summary, our study unveils the critical role of kidney CD8Trms in contributing to salt-sensitive hypertension and its recurrence. This leads to targeting key molecules that initiate the development of Trms to mitigate the persistency of hypertension.