Abstract 245: Role of Endogenous T Cell Receptors in the Development of Hypertension

Abstract

The purpose of this investigation was to determine if endogenous T cell receptors (TCR) are required for the development of hypertension. Our laboratory has preliminary data suggesting that hypertension is associated with an oligoclonal TCR expansion of CD8+ T cells in mouse kidney. To determine whether mice with an altered TCR phenotype are protected against hypertension, OT1 mice, which express a transgenic TCR specific for ovalbumin on CD8+ cells, and OT1xRag-1-/- mice were infused with angiotensin II (490ng/min/kg) or vehicle. Blood pressure was measured by telemetery. After 2 weeks OT1 mice infused with angiotensin II exhibited increased blood pressure (171 ± 10 systolic, 113 ± 16 diastolic, mean ± S.E.M. mmHg) compared to controls (117 ± 15 systolic, 83 ± 7 diastolic). The hypertensive response was blunted in OT1xRag-1-/- mice that received angiotensin II (142 ± 12 systolic, 85 ± 13 diastolic). Analysis of kidney resident CD8+ TCR by flow cytometery revealed that 6.8 ± 2.9% and 5.2 ± 1.7% in sham and angiotensin II treated OT1 mice respectively were non-transgenic whereas 0.3 ± 0.2% and 0.5 ± 0.1% in sham and angiotensin II treated OT1xRag-1-/- mice respectively were non-transgenic. These data together with the finding that hypertension promotes an oligoclonal TCR expansion in kidney suggest that endogenous TCR are required to respond to neoantigens and mediate the development of overt hypertension.