{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:21:20Z","timestamp":1790637680424,"version":"4.1.0"},"reference-count":34,"publisher":"Open Exploration Publishing","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/doi.org\/10.37349\/Open_Exploration_Crossmark_Policy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Aim: Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with activated CD4+ T cells and autoantibodies to angiotensin II type 1 receptor (AT1-AA). We have previously shown that CD4+ T cells isolated from women with PE cause hypertension, increased tumor necrosis factor alpha (TNF-\u03b1), endothelin-1, and soluble fms-like tyrosine kinase-1 (sFlt-1) when injected into pregnant nude-athymic rats compared to CD4+ T cells from normal pregnant (NP) women. However, the role of PE CD4+ T cells to cause AT1-AA as a mechanism of hypertension is not known. Our goal was to determine if PE CD4+ T cells stimulate AT1-AA in pregnant nude-athymic rats.\nMethods: CD4+ T cells were isolated from human NP and PE placentasand injected into nude-athymic rats on gestational day (GD) 12. In order to examine the role of the PE CD4+ T cells to stimulate B cell secretion of AT1-AA, a subset of the rats receiving PE CD4+ T cells were treated with rituximab on GD 14 or anti-CD40 ligand (anti-CD40L) on GD 12. On GD 19, mean arterial pressure (MAP) and tissues were obtained. \nResults: MAP [114 \u00b1 1 mmHg (n = 9)] and AT1-AA [19.8 \u00b1 0.9 beats per minute (bpm, n = 4)] were increased in NP nude + PE CD4+ T cells compared to NP nude + NP CD4+ T cells [98 \u00b1 2 mmHg (n = 7, P &lt; 0.05) and 1.3 \u00b1 0.9 bpm (n = 5, P &lt; 0.05)]. Rituximab (103 \u00b1 2 mmHg, n = 3, P &lt; 0.05) and anti-CD40L (102 \u00b1 1 mmHg, n = 3, P &lt; 0.05) lowered MAP compared to NP nude + PE CD4+ T cells. Circulating a proliferation-inducing ligand (APRIL) and placental angiotensin-converting enzyme 2 (ACE-2) activity was increased in response to PE CD4+ T cells. \nConclusions: These results show that placental CD4+ T cells play an important role in the pathophysiology of PE, by activating B cells secreting AT1-AA to cause hypertension during pregnancy.<\/jats:p>","DOI":"10.37349\/emed.2022.00077","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T08:57:40Z","timestamp":1645779460000},"page":"99-111","update-policy":"https:\/\/doi.org\/10.37349\/open_exploration_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Placental CD4+ T cells from preeclamptic patients cause autoantibodies to the angiotensin II type I receptor and hypertension in a pregnant rat model of preeclampsia"],"prefix":"10.37349","author":[{"given":"Kristin E.","family":"Reeve","sequence":"first","affiliation":[{"name":"1 Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangeline","family":"Deer","sequence":"additional","affiliation":[{"name":"2 Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena M.","family":"Amaral","sequence":"additional","affiliation":[{"name":"2 Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise C.","family":"Cornelius","sequence":"additional","affiliation":[{"name":"2 Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 39216, USA 3 Department of Emergency Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen","family":"Herrock","sequence":"additional","affiliation":[{"name":"2 Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlyn C.","family":"Harmon","sequence":"additional","affiliation":[{"name":"2 Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Campbell","sequence":"additional","affiliation":[{"name":"2 Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"2 Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"2 Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Wallukat","sequence":"additional","affiliation":[{"name":"4 Experimental and Clinical Research Center, Max-Delbr\u00fcck-Centrum f\u00fcr Molekulare Medizin, 13092 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Dechend","sequence":"additional","affiliation":[{"name":"4 Experimental and Clinical Research Center, Max-Delbr\u00fcck-Centrum f\u00fcr Molekulare Medizin, 13092 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babbette","family":"LaMarca","sequence":"additional","affiliation":[{"name":"2 Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"21850","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"American College of Obstetricians and Gynecologists. 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