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

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.