Sex differences in proinflammatory Th1 cell kidney infiltration in ANG II-induced hypertension

T cells are required for the development of hypertension in male and postmenopausal female mice, while premenopausal females are protected from T cell-mediated hypertension. In addition, Angiotensin II (ANG II) infusion induces pro-inflammatory response in the kidneys of postmenopausal females, suggesting that the protective role of estrogen implicates the modulation of the immune response. Previous studies identified the participation of Th1, Th17, and Treg CD4+ lymphocytes in hypertension. However, little is known about the role of Th2 cells and humoral immunity in hypertension. To better understand sex differences in the immune cell mediated hypertensive response, we sought to determine if there were significant differences in the immune cell profiles of premenopausal female and age-matched male mice following ANG II-infusion. 12-week-old male and female C57BL/6 mice were infused with ANG II (800ng/kg/day) via osmotic minipump. Systolic blood pressure (SBP) was measured via tail cuff. Spleens, kidneys and whole blood were collected for flow cytometric analysis of T cell pro-inflammatory subtypes (T-bet+ Th1, Gata3+ Th2, Rorgt+ Th17, and Foxp3+ Treg). Female mice had an expected blunted SBP response to ANG II infusion (day 12: female ANG II ∆3 ± 5 mmHg, ns vs. control). However, ANG II caused a significant increase in SBP in male mice (day 13: male ANG II-infused ∆25 ± 7 mmHg, *p≤0.05 vs. control). Following 14 days of ANG II infusion, there was a significant increase in Th17 cells in male kidneys (male ANG II 7414 ± 661 vs control male 4572 ± 138 *p≤0.05 vs. male control), with no change in splenic Th17 populations. Following 22 days of ANG-II induced hypertension, there was a significant increase in the frequency of Th1 in the kidneys of male mice (male ANG II 80.8% ± 1.4% vs. male control 31% ± 8.1%, *p≤0.05), with no increase in splenic populations (male ANG II 0.9% ± 0.2% vs. male control 0.7 ± 0.2%, ns). At day 22, there was also a significant increase in Th2 lymphocytes in male kidneys following ANG II-infusion (male ANG II 8.6% ± 0.8% vs. male control 4.6% ± 0.6%, *p≤0.05) and Th17 lymphocytes remained elevated (male ANG II 8.2% ± 1.0% vs. male control 3.7 ± 0.6%, *p≤0.05). In contrast, following 14 days of ANG II infusion, there was a significant increase in Th2 cells in the female kidneys (female ANG II 20.9% ± 4.0% vs. female control 13.5 ± 1.3%, *p≤0.05) with no change in splenic Th2 populations. Following 22 days of ANG II infusion, there were no significant increases in the female kidney of Th1, Th2 or Th17 T cell pro-inflammatory subtypes. Thus, female resistance to ANG II-induced hypertension is associated with a reduced infiltration of proinflammatory CD4+ T cells into the kidney. RO1 NS110749 RO1 DK083785 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.