Abstract 12: Regulation of Hypertension by Sex specific T Cell Subtypes

Background: Studies in humans and animal models of hypertension indicate arterial pressure is modulated by distinct T cell populations. Recombination activating gene-1 (Rag1)-deficient mice lack B and T cells and exhibit lower mean arterial pressure (MAP) than wild type mice during angiotensin II (Ang II) -induced hypertension. Adoptive transfer of splenic T cells from male wild type (WT) mice restores the Ang II-dependent hypertension in male Rag1 mice. Objective: This study investigated the impact of the sex of the T cell donor on T cell modulation of blood pressure during Ang II-induced hypertension in the male Rag1 mouse in order to gain insight into the mechanisms contributing to sex differences in hypertension. Method: Mature CD8 + T cells were isolated using flow cytometry from male ( CD8 M ) and female ( CD8 F ) C57/Bl6 WT mice and injected into the jugular vein (8 x 10 6 T cells/mouse) of male Rag1 mice. Three weeks later, radiotransmitters were implanted and MAP was recorded before and after Ang II (490 ng/min/kg) was infused by osmotic minipump for two weeks. Once the experiment was terminated, T cell subpopulation frequencies in the spleen and kidney were assessed by fluorescence activated cell sorting, immunohistochemistry and real-time PCR. Results: Adoptive transfer of CD8 M restored the magnitude of the Ang II-induced hypertension to WT levels in male Rag1 mice. In contrast, adoptive transfer of CD8 F attenuated the hypertension [peak MAP (mm Hg): WT 143 ± 4.1; Rag1, 127 ± 2.8*; Rag1+CD8 M , 142 ± 4.0; Rag1+CD8 F , 120 ± 4.0*; n=10-12/group *p + CD4 + T regulatory ( Treg ) cells in the male WT mouse spleen than in female spleens in the whole mature T cell population [Treg (%): Male, 3.2 ± 0.4 vs Female, 5.2 ± 0.3; p + CD125 + Treg cells in the CD4 + population after adoptive transfer of CD8 M compared to CD8 F in male Rag 1 mice [Treg (%): Rag1+CD8 M , 9.7 ± 1.4 vs CD8 F , 14.7 ± 1.7; p Conclusions: This study suggests sex differences in the Treg population contributes to why men have higher MAP than women up through the fifth decade of life.