Abstract 020: Sex Difference in T Regulatory Cells After Adoptive Transfer From Hypertensive Donors Leads to Protection Against T Cell-Mediated Hypertension in Premenopausal Female Mice

Abstract

Activation of T cell-dependent pro-inflammatory responses are required for Ang II hypertension in male mice. However, females are protected from T cell-mediated hypertension and may suppress hypertension by directly preventing Ang II-induced pro-inflammatory T cell activation. Here we sought to determine whether transferring T cells from hypertensive donor mice eliminates female protection against T cell-mediated hypertension. Splenic CD3 + T cells were transferred from normotensive (NT) or Ang II-hypertensive (HT) C57BL/6J male donors to female Rag-1 -/- (NT T cell female-NTF; HT T cell female-HTF) or male Rag-1 -/- (HT T cell male-HTM) recipient mice. Blood pressure was monitored (tail cuff) for 5 weeks post-transfer. Ang II (490ng/kg/min) was infused into recipient mice for 14 days during weeks 4 and 5 post-transfer (NTFA; HTFA; HTMA). Ang II significantly increased MAP in donor male mice (NT 114 vs HT 157 mmHg, p<0.05). Transfer of T cells from HT donors did not induce HT in female or male recipients. Similarly, T cell donor environment did not affect Ang II-induced blood pressure in female recipients, which remained protected compared to male recipients (MAP: NTF 83 + 4 mmHg*, HTF 88 + 6 mmHg*, NTFA 101 + 5 mmHg*, HTFA 103 + 5 mmHg*, HTMA 138 + 3 mmHg, *p<0.05 vs HTMA). Flow cytometry demonstrated similar splenic T cell frequency across all groups (CD3: NTF 18%, NTFA 16%, HTF 17%, HTFA 14%, HTMA 18%, p>0.05). However, regulatory T cells were significantly reduced in male recipients compared to all female groups (Foxp3: NTF 21.6%*, NTFA 22.2%*, HTF 22.8%*, HTFA 22.6%*, HTMA 15.3%, *p<0.05 vs HTMA) Females had significantly less renal T cell infiltration compared to males and infiltration was not impacted by Ang II infusion or T cell donor status (CD3: NTF 12,083*, NTFA 11,317*, HTF 12,656*, HTFA 8,997*, HTMA 22,405, *p<0.05 vs HTMA; CD4: NTF 6,411*, NTFA 4,702*, HTF 5,831*, HTFA 4,579*, HTMA 9,914, *p<0.05 vs HTMA; CD8: NTF 5,397*, NTFA 6,123*, HTF 6,362*, HTFA 3,792*, HTMA 11,727, *p<0.05 vs HTMA). These results demonstrate that female mice prevent T cell-mediated hypertension and renal T cell infiltration regardless of previous T cell exposure to a hypertensive environment, suggesting a direct preventive mechanism in females against pro-hypertensive T cell responses.