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Oligoclonal CD8+ T cells play a critical role in the development of hypertension.
- Source :
-
Hypertension (Dallas, Tex. : 1979) [Hypertension] 2014 Nov; Vol. 64 (5), pp. 1108-15. Date of Electronic Publication: 2014 Aug 04. - Publication Year :
- 2014
-
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.<br /> (© 2014 American Heart Association, Inc.)
- Subjects :
- Adaptive Immunity physiology
Angiotensin II adverse effects
Angiotensin II pharmacology
Animals
CD4 Antigens genetics
CD4 Antigens physiology
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes pathology
CD4-Positive T-Lymphocytes physiology
CD8 Antigens genetics
CD8 Antigens physiology
CD8-Positive T-Lymphocytes immunology
Disease Models, Animal
Endothelium, Vascular drug effects
Endothelium, Vascular physiopathology
Homeodomain Proteins genetics
Homeodomain Proteins physiology
Hypertension chemically induced
Kidney blood supply
Major Histocompatibility Complex genetics
Major Histocompatibility Complex physiology
Male
Mice
Mice, Knockout
Vascular Remodeling drug effects
CD8-Positive T-Lymphocytes pathology
CD8-Positive T-Lymphocytes physiology
Hypertension pathology
Hypertension physiopathology
Kidney immunology
Kidney pathology
Oligoclonal Bands physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4563
- Volume :
- 64
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Publication Type :
- Academic Journal
- Accession number :
- 25259750
- Full Text :
- https://doi.org/10.1161/HYPERTENSIONAHA.114.04147