Key result
T cells from treatment-resistant hypertension worsen hypertension and endothelial dysfunction via TNF in mice.
Why the study?
Preclinical studies suggest a pivotal role of T cells in hypertension, but definitive evidence for a causal role of T cells in the development of human hypertension was lacking.
Do T cells from patients with treatment-resistant hypertension directly modulate blood pressure and vascular function in vivo in humanized mice?
Do T cells from patients with treatment-resistant hypertension directly modulate blood pressure and vascular function in vivo in humanized mice?
T cells from patients with treatment-resistant hypertension promote an exaggerated hypertensive response and endothelial dysfunction in humanized mice via TNF-mediated mechanisms, suggesting a causal role of T cell-derived TNF in human hypertension.
T cells from TRH patients exacerbate AngII hypertension and endothelial dysfunction via TNF in humanized mice; leaves open whether TNF or T-cell targeting alters outcomes in patients.
Aims Preclinical studies suggest a pivotal role of adaptive immunity, particularly T cells, in hypertension. However, due to the multifactorial pathogenesis, there is still no definitive evidence for a causal role of T cells in the development of hypertension in humans. We sought to determine whether T cells from patients with treatment-resistant hypertension (TRH) directly modulate blood pressure and vascular function in vivo. Methods and Results Peripheral blood mononuclear cells (PBMCs) from TRH patients and healthy controls (HC) were adoptively transferred into immunodeficient NSG-(KbDb)^null mice. Hypertension was induced by angiotensin II infusion for 14 days and monitored continuously by radiotelemetry. Following T cell engraftment, blood pressure was assessed at baseline and during AngII infusion in both groups of recipient mice. At baseline, systolic blood pressure did not differ between both groups. However, mice receiving TRH-PBMCs developed a significantly higher systolic blood pressure following AngII compared with HC-PBMC recipients. Endothelial dysfunction in isolated perfused kidneys was more pronounced in AngII-challenged TRH-PBMC recipients compared to HC-PBMC recipients. TRH-PBMC recipients displayed elevated effector memory CD4+ T cells and Th17 frequencies in spleen and kidney, along with markedly increased renal expression of human T cell-derived TNF. Overnight incubation of mouse aortic rings with human TNF induced endothelial dysfunction, indicating a causal role of T cell-derived TNF. As a proof of concept, TNF inhibition attenuated AngII-induced hypertension in TRH-PBMC–engrafted mice. Conclusions T cells from patients with treatment-resistant hypertension promote an exaggerated hypertensive response and endothelial dysfunction in PBMC-engrafted humanized mice, promoted by TNF-mediated mechanisms. These findings provide evidence that T cell–derived TNF may contribute to the pathogenesis of human hypertension.
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Rahman et al. (2026) studied Treatment-resistant hypertension. Adoptive transfer of PBMCs from treatment-resistant hypertension patients vs. Adoptive transfer of PBMCs from healthy controls was evaluated on Systolic blood pressure and endothelial dysfunction following angiotensin II infusion. T cells from treatment-resistant hypertension patients promoted significantly higher systolic blood pressure and endothelial dysfunction during 14-day AngII infusion via TNF in humanized mice.
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