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Oligoclonal CD8 + cells in the kidney mediate experimental hypertension (1074.5)
Author(s) -
Trott Daniel,
Thabet Salim,
Itani Hana,
Wu Jing,
Norlander Allison,
Chen Wei,
Harrison David
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1074.5
Subject(s) - cd8 , t cell receptor , kidney , medicine , endocrinology , spleen , biology , immunology , cytotoxic t cell , t cell , immune system , chemistry , biochemistry , in vitro
We have shown that T cells are involved in the genesis of hypertension, but the subset(s) involved have not been defined. T cell activation involves clonal expansion of cells with unique T cell receptors (TCRs). We analyzed TCR usage in mice infused with Ang II for two weeks. Ang II did not affect TCR profiles in the spleen, mesenteric vasculature or kidney CD4 + cells but markedly skewed the TCR profile in 3 V families of CD8 + cells in the kidney. This suggests an oligoclonal T cell response in hypertension. To further examine the role of CD8 + cells in hypertension we examined the hypertensive response to Ang II in CD4 ‐/‐ and CD8 ‐/‐ mice. After two weeks of Ang II, wild type and CD4 ‐/‐ mice systolic blood pressure rose to 172 ± 5.7 mmHg and 176 ± 6.3 mmHg, respectively. This response was blunted in CD8 ‐/‐ mice (146 ± 5.9 mmHg). To determine whether a full repertoire of CD8 + TCRs are required for hypertension we studied OT1 x RAG‐1 ‐/‐ mice, which have a TCR on CD8 + cells that is restricted to an ovalbumin peptide. Importantly, these mice cannot generate other TCRs. OT1 x RAG‐1 ‐/‐ mice demonstrated a blunted hypertensive response to Ang II (141 ± 7.8 mmHg) which was similar to that observed in CD8 ‐/‐ mice. We conclude that hypertension requires a full repertoire of CD8 + TCR, from which select populations of cells proliferate and accumulate in the kidney. These cells likely release mediators that promote salt and water retention and hypertension.