Medical College of Wisconsin
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Oligoclonal CD8+ T cells play a critical role in the development of hypertension. Hypertension 2014 Nov;64(5):1108-15

Date

09/27/2014

Pubmed ID

25259750

Pubmed Central ID

PMC4191997

DOI

10.1161/HYPERTENSIONAHA.114.04147

Scopus ID

2-s2.0-84919714927   107 Citations

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 CD4(-/-) and MHCII(-/-) mice was similar to that observed in wild-type mice, whereas CD8(-/-) mice and OT1xRAG-1(-/-) 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-1(-/-) 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 CD4(-/-) mice infused with angiotensin II retained water and sodium, whereas CD8(-/-) mice did not. CD8(-/-) 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.

Author List

Trott DW, Thabet SR, Kirabo A, Saleh MA, Itani H, Norlander AE, Wu J, Goldstein A, Arendshorst WJ, Madhur MS, Chen W, Li CI, Shyr Y, Harrison DG



MESH terms used to index this publication - Major topics in bold

Adaptive Immunity
Angiotensin II
Animals
CD4 Antigens
CD4-Positive T-Lymphocytes
CD8 Antigens
CD8-Positive T-Lymphocytes
Disease Models, Animal
Endothelium, Vascular
Homeodomain Proteins
Hypertension
Kidney
Major Histocompatibility Complex
Male
Mice
Mice, Knockout
Oligoclonal Bands
Vascular Remodeling