Oligoclonal CD8+ T cells play a critical role in the development of hypertension

Daniel W. Trott, Salim R. Thabet, Annet Kirabo, Mohamed A. Saleh, Hana Itani, Allison E. Norlander, Jing Wu, Anna Goldstein, William J. Arendshorst, Meena S. Madhur, Wei Chen, Chung I. Li, Yu Shyr, David G. Harrison

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Abstract

Recent studies have emphasized a role of adaptive immunity, and particularly T cells, in the genesis of hypertension. We sought to determine the T-cell subtypes that contribute to hypertension and renal inflammation in angiotensin II-induced hypertension. Using T-cell receptor spectratyping to examine T-cell receptor usage, we demonstrated that CD8+ cells, but not CD4+ cells, in the kidney exhibited altered T-cell receptor transcript lengths in Vβ3, 8.1, and 17 families in response to angiotensin II-induced hypertension. Clonality was not observed in other organs. The hypertension caused by angiotensin II in CD4CD25-/- and MHCIICD25-/- mice was similar to that observed in wild-type mice, whereas CD25-/- mice and OT1xRAG-1CD25-/- mice, which have only 1 T-cell receptor, exhibited a blunted hypertensive response to angiotensin II. Adoptive transfer of pan T cells and CD8+ T cells but not CD4+/CD25- cells conferred hypertension to RAG-1CD25-/- mice. In contrast, transfer of CD4+/CD25+ cells to wild-type mice receiving angiotensin II decreased blood pressure. Mice treated with angiotensin II exhibited increased numbers of kidney CD4+ and CD8+ T cells. In response to a sodium/volume challenge, wild-type and CD4CD25-/- mice infused with angiotensin II retained water and sodium, whereas CD25-/- mice did not. CD25-/- mice were also protected against angiotensin-induced endothelial dysfunction and vascular remodeling in the kidney. These data suggest that in the development of hypertension, an oligoclonal population of CD8+ cells accumulates in the kidney and likely contributes to hypertension by contributing to sodium and volume retention and vascular rarefaction.

Original languageEnglish
Pages (from-to)1108-1115
Number of pages8
JournalHypertension
Volume64
Issue number5
DOIs
Publication statusPublished - 2014 Nov 1

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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    Trott, D. W., Thabet, S. R., Kirabo, A., Saleh, M. A., Itani, H., Norlander, A. E., Wu, J., Goldstein, A., Arendshorst, W. J., Madhur, M. S., Chen, W., Li, C. I., Shyr, Y., & Harrison, D. G. (2014). Oligoclonal CD8+ T cells play a critical role in the development of hypertension. Hypertension, 64(5), 1108-1115. https://doi.org/10.1161/HYPERTENSIONAHA.114.04147