Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Department of Physiology, Augusta University and the Medical College of Georgia, Augusta, GA, USA.
Exp Physiol. 2020 May;105(5):864-875. doi: 10.1113/EP088340. Epub 2020 Mar 17.
What is the central question of this study? Recruitment of immune cells to the kidney potentiates hypertensive pathology, but more refined methods are needed to assess these cells functionally. Adoptive transfer studies of immune cells have been limited in rat models and especially in the study of salt-sensitive hypertension. We tested the hypothesis that splenocyte transfer into T-cell-deficient rats is sufficient to exacerbate salt-sensitive hypertension. What is the main finding and its importance? We demonstrate that transfer of splenocytes into T-cell-deficient animals exacerbates salt-sensitive hypertension, and an enrichment in the CD4 compartment specifically induces this phenomenon.
Increasing evidence of immune system activation during the progression of hypertension and renal injury has led to a need for new methods to study individual cell types. Transfer of immune cells serves as a powerful tool to isolate effects of specific subsets. Transfer studies in Rag1 mice have demonstrated an important role of T-cell activation in hypertension, but this approach has yielded limited success in rat models. Using the T-cell-deficient Dahl salt-sensitive (SS) rat, SS , we hypothesized that splenocyte transfer from SS wild-type animals into SS animals would populate the T-cell compartment. The Dahl SS background provides a model for studying salt-sensitive hypertension; therefore, we also tested whether the dietary salt content of the donor would confer differential salt sensitivity in the recipient. To test this, donors were maintained on either a low-salt or a high-salt diet, and at postnatal day 5 the recipients received splenocyte transfer from one of these groups before a high-salt diet challenge. We showed that splenocyte transfer elevated blood pressures while rats were fed low salt and exacerbated the salt-sensitive increase in pressure when they were fed fed high salt. Furthermore, transfer of splenocytes conferred exacerbated renal damage. Lastly, we confirmed the presence of T cells in the circulation and in the spleen, and that infiltration of immune cells, including T cells, macrophages and B cells, into the kidney was elevated in those receiving the transfer. Interestingly, the source of the splenocytes, from donors fed either a low-salt or a high-salt diet, did not significantly affect these salt-sensitive phenotypes.
本研究的核心问题是什么？免疫细胞向肾脏的募集增强了高血压病理，但需要更精细的方法来评估这些细胞的功能。免疫细胞的过继转移研究在大鼠模型中受到限制，尤其是在盐敏感型高血压的研究中。我们测试了这样一个假设，即脾细胞转移到 T 细胞缺陷大鼠中足以加重盐敏感型高血压。主要发现及其重要性是什么？我们证明，将脾细胞转移到 T 细胞缺陷动物中会加剧盐敏感型高血压，而 CD4 区室的富集特异性地诱导了这种现象。
越来越多的证据表明，免疫系统在高血压和肾脏损伤进展过程中的激活导致需要新的方法来研究单个细胞类型。免疫细胞的转移可作为分离特定亚群作用的有力工具。Rag1 小鼠中的转移研究表明 T 细胞活化在高血压中起重要作用，但这种方法在大鼠模型中取得的成功有限。利用 T 细胞缺陷型 Dahl 盐敏感（SS）大鼠，我们假设来自 SS 野生型动物的脾细胞转移到 SS 动物中会使 T 细胞区室充满细胞。Dahl SS 背景为研究盐敏感型高血压提供了模型；因此，我们还测试了供体的饮食盐含量是否会在受体中赋予不同的盐敏感性。为此，供体维持在低盐或高盐饮食，在出生后第 5 天，受体接受来自其中一组的脾细胞转移，然后接受高盐饮食挑战。我们表明，脾细胞转移会在大鼠低盐饮食时升高血压，并在高盐饮食时加剧盐敏感型血压升高。此外，脾细胞转移会加重肾脏损伤。最后，我们证实了循环和脾脏中存在 T 细胞，并且接受转移的免疫细胞（包括 T 细胞、巨噬细胞和 B 细胞）浸润到肾脏中增加。有趣的是，来自低盐或高盐饮食供体的脾细胞来源并没有显著影响这些盐敏感表型。
