Abstract 5: Angiotensin II-induced Alterations of T Cell Receptor Vβ Chain Usage in Kidney and Mesenteric Vasculature
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. 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, T cells with multiple TCRs proliferate. We sought to determine if hypertension promotes a mono- or polyclonal T cell response. TCR Vβ chain gene transcript length can be used to examine T cell clonality. 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. PCR was employed to amplify the 24 TCR Vβ chain subfamilies in the kidney and mesenteric vasculature. PCR products were subjected to high-resolution capillary electrophoresis fragment analysis to determine TCR Vβ chain transcript length. Eleven of the 24 Vβ length profiles exhibited greater than 20% skewing with angiotensin II infusion in kidney and 6 of 24 exhibited greater than 20% skewing in mesentery. Dominant transcript lengths were present with angiotensin II infusion for Vβ 1 (30 ± 5 vs. 51 ± 7), 3 (29 ± 3 vs. 51 ± 12) and 20 (0 ± 0 vs. 41 ± 18) in kidney and 1 (30 ± 2 vs. 43 ± 4), 4 (27 ± 4 vs. 45 ± 3) and 20 (15 ± 3 vs. 46 ± 6) in mesentery (data are expressed as % ± S.E.M. of TCR transcripts of a given length within each Vβ family, sham vs. angiotensin II, n = 5 per group). These results suggest that hypertension results in oligoclonal T cell expansion in the kidney and mesentery. Alterations in Vβ 1 and 20 in both kidney and mesentery suggest a common TCR response between tissues.
- © 2012 by American Heart Association, Inc.