Oligoclonal CD8 + T Cells Play a Critical Role in the Development of Hypertension (original) (raw)
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 (TCR) spectratyping to examine TCR usage we demonstrated that CD8 + cells, but not CD4 + cells, in the kidney exhibited altered TCR 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 WT mice, while CD8 −/− mice and OT1xRAG-1 −/− mice, which have only one TCR, exhibited a blunted hypertensive response to angiotensin II. Adoptive transfer of panT 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 angiotensininduced endothelial dysfunction and vascular remodeling in the kidney. These data suggest that in the development of hypertension, an oligoclonal population of CD8 + cells accumulate in the kidney and likely contribute to hypertension by contributing to sodium and volume retention and vascular rarefaction.
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