Sex differences in T-lymphocyte tissue infiltration and development of angiotensin II hypertension.
Sex differences in T-lymphocyte tissue infiltration and development of angiotensin II hypertension.
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DOI：
10.1161/hypertensionaha.114.03581
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Hay M
中科院分区：
文献类型：
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作者：
Pollow DP;Uhrlaub J;Romero-Aleshire M;Sandberg K;Nikolich-Zugich J;Brooks HL;Hay M
有大量证据表明，免疫系统的激活是必要的，并要求在男性血管紧张素II诱导的高血压的发展。本研究的目的是确定是否存在性别差异的适应性免疫系统诱导血管紧张素II依赖性高血压的能力，以及是否中央和肾脏T细胞浸润血管紧张素II诱导的高血压是性别依赖性的。使用了缺乏T和B细胞的Rag-1−/−小鼠。雄性和雌性Rag-1−/−小鼠在14天Ang II输注（490 ng/kg/min）前3周接受雄性CD 3 + T细胞的过继转移。通过尾套监测血压。在缺乏T细胞的情况下，收缩压（SBP）对Ang II的反应在性别之间相似（男性Δ22.1mmHg vs女性Δ 18 mmHg）。在过继性转移雄性T细胞后，Ang II显著增加男性SBP（Δ37.7mmHg，p<0.05），而女性SBP（Δ13.7mmHg，p<0.05）。对总T细胞和CD 4+、CD 8+和调节性Foxp 3 +-CD 4 + T细胞亚群的流式细胞术分析表明，在对照组和输注Ang II的动物中，与雌性动物相比，雄性动物的肾淋巴细胞浸润显著增加（p<0.05）。与雌性动物相比，雄性动物脑SFO区域中CD 3+阳性T细胞的免疫组织化学染色增加。这些结果表明，与雄性小鼠相比，雌性Rag-1−/−小鼠免受雄性T细胞介导的Ang II诱导的高血压增加的影响，这种保护可能涉及肾脏和大脑T细胞浸润程度的性别差异。
There is extensive evidence that activation of the immune system is both necessary and required for the development of Ang II-induced hypertension in males. The purpose of this study was to determine if sex differences exist in the ability of the adaptive immune system to induce Ang II-dependent hypertension and whether central and renal T cell infiltration during Ang II-induced hypertension is sex-dependent. Rag-1−/− mice, lacking both T and B cells, were used. Male and female Rag-1−/− mice received adoptive transfer of male CD3+ T cells 3 weeks prior to 14 day Ang II infusion (490ng/kg/min). Blood pressure was monitored via tail cuff. In the absence of T cells, systolic blood pressure (SBP) responses to Ang II were similar between sexes (Δ22.1mmHg males vs. Δ18mmHg females). After adoptive transfer of male T cells, Ang II significantly increased SBP in males (Δ37.7mmHg, p<0.05) compared to females (Δ13.7mmHg). Flow cytometric analysis of total T cells and CD4+, CD8+, and regulatory Foxp3+-CD4+ T cell subsets identified that renal lymphocyte infiltration was significantly increased in males vs females in both control and Ang II infused animals (p<0.05). Immunohistochemical staining for CD3+ positive T cells in the SFO region of the brain was increased in males compared to females. These results suggest that female Rag-1−/− mice are protected from male T cell-mediated increases in Ang II-induced hypertension as compared to their male counterparts, and this protection may involve sex differences in the magnitude of T cell infiltration of the kidney and brain.