Alterations of T cell receptor Vβ chain usage in angiotensin IIinduced hypertension

Abstract

Stimulation of the T cell receptor (TCR) with a specific antigen leads to clonal expansion of cells with identical TCRs. In contrast, if multiple antigens are presented, the T cells with multiple TCRs proliferate. We have previously shown that T cells play a critical role in the genesis of hypertension, and that activated T cells infiltrate the vasculature and the kidney to promote vasoconstriction and sodium retention. We sought to determine if hypertension promotes a mono‐ or polyclonal T cell response. We produced hypertension in C57Bl/6 mice by chronic (2 week, 490 ng/kg/min) infusion of angiotensin II and used vehicle infused mice as controls. Nested PCR was employed to identify TCR subfamilies of the Vβ chain in the kidney and vasculature. Only 4 of the 24 Vβ chain subfamilies were present in >50% of kidneys from controls, whereas 12 of the 24 were present in >50% of the kidneys from angiotensin II infused mice. Notably, Vβ4 was present in 2 of 8 sham and 6 of 8 Ang II samples and Vβ17 was present in 1 of 8 sham and 5 of 8 Ang II samples. In mesenteric vessels, 18 of 24 Vβ subfamilies were present in >50% of samples from controls and 15 of 24 were present in >50% of samples from Ang II samples. These results suggest that hypertension results in polyclonal T cell expansion in the kidney, likely due to the generation of multiple neoantigens.