CD8 T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension.

Recent studies suggest a role for T lymphocytes in hypertension. However， whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular， CD8 T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8 T cell-injected mice， leading to up-regulation of the Na-Cl co-transporter NCC， p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8 T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase， up-regulation of the K channel Kir4.1， and stimulation of the Cl channel ClC-K. The last event increases chloride efflux， leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively， these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension.