Recent studies indicate that T cells can modulate arterial pressure. We found that adoptive transfer of male but not female CD3+, CD4+ and CD8+ T cells can mediate Ang II-dependent hypertension in male Rag1 deficient mice. These observations indicate sex specific ations of T cells determine resistance and vulnerability in the regulation of hypertension by the immune system.
In aim 1, we will determine if T cell-mediated susceptibility and resistance to hypertension induced by Ang II infusion in the male Rag1-/- host is due to gonad-dependent or gonad-independent effects of the sex chromosomes (XX vs XY) on the T cell donor and how these effects link to end organ damage and T cell responses.
In aim 2, we will determine if sex-specific T cell subset responses to Ang II infusion in the male Rag1-/- host are due to sex differences in T cell angiotensin type 1 and type 2 receptors (AT1R and AT2R) and how these receptor- mediated T cell effects link to blood pressure, end organ damage and T cell function.
Aim 3 will determine the role of pro- and anti-inflammatory cytokines in CD4+ and CD8+- mediated susceptibility and resistance to Ang II-induced hypertension and link these findings to end organ damage. Defining the mechanisms by which T cell sub- specification and T cell function are regulated by sex in a model of Ang II-dependent hypertension may provide an explanation for the delayed onset of hypertension in premenopausal women compared with age-matched men. Furthermore, discovering immune regulatory phenotypes associated with resistance and susceptibility to hypertension induced by Ang II could uncover T cell subset specific targets and strategies for treating hypertension in both sexes.

Public Health Relevance

Hypertension is the number one risk factor for cardiovascular and kidney disease throughout the world. The age of onset occurs later in women than men suggesting females are protected from the development of hypertension. Recent studies indicate that T cells (a group of white blood cells that play a central role in immunity) contribut to hypertension. We have discovered that a male T cell subset contributes to hypertension while a female T cell subset attenuates hypertension. Using a unique animal model, in which we can separate the effects of the sex chromosomes (XY vs XX) from the hormonal differences between males and females (e.g., testosterone vs estrogen), we propose to investigate the mechanisms by which female T cells protect males from hypertension. We expect this research to ultimately lead to novel therapeutic interventions for hypertensive disease in both men and women.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Hypertension and Microcirculation Study Section (HM)
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OH, Youngsuk
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Georgetown University
Internal Medicine/Medicine
Schools of Medicine
United States
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Sandberg, Kathryn; Wright, Stephen P; Umans, Jason G (2018) Activity Tracking's Newest Companion: Pulse Wave Velocity. Hypertension 72:294-295
Pai, Amrita V; Maddox, Taylor; Sandberg, Kathryn (2018) T Cells and Hypertension: Solved and Unsolved Mysteries Regarding the Female Rat. Physiology (Bethesda) 33:254-260
de Souza, Aline Maria Arlindo; West, Crystal A; de Abreu, Aline Rezende Ribeiro et al. (2018) Role of the Renin Angiotensin System in Blood Pressure Allostasis-induced by Severe Food Restriction in Female Fischer rats. Sci Rep 8:10327
Arnold, Arthur P; Cassis, Lisa A; Eghbali, Mansoureh et al. (2017) Sex Hormones and Sex Chromosomes Cause Sex Differences in the Development of Cardiovascular Diseases. Arterioscler Thromb Vasc Biol 37:746-756
Ji, Hong; Pai, Amrita V; West, Crystal A et al. (2017) Loss of Resistance to Angiotensin II-Induced Hypertension in the Jackson Laboratory Recombination-Activating Gene Null Mouse on the C57BL/6J Background. Hypertension 69:1121-1127
Miller, Leah R; Marks, Cheryl; Becker, Jill B et al. (2017) Considering sex as a biological variable in preclinical research. FASEB J 31:29-34
Wright, Stephen P; Hall Brown, Tyish S; Collier, Scott R et al. (2017) How consumer physical activity monitors could transform human physiology research. Am J Physiol Regul Integr Comp Physiol 312:R358-R367
McGregor, Alyson J; Hasnain, Memoona; Sandberg, Kathryn et al. (2016) How to study the impact of sex and gender in medical research: a review of resources. Biol Sex Differ 7:46
Oh, Young S; Appel, Lawrence J; Galis, Zorina S et al. (2016) National Heart, Lung, and Blood Institute Working Group Report on Salt in Human Health and Sickness: Building on the Current Scientific Evidence. Hypertension 68:281-8
Sandberg, Kathryn; Ji, Hong; Einstein, Gillian et al. (2016) Is immune system-related hypertension associated with ovarian hormone deficiency? Exp Physiol 101:368-74

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