PMID- 37645383
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230901
IS  - 2692-3106 (Electronic)
IS  - 2692-3106 (Linking)
VI  - 3
IP  - 1
DP  - 2022
TI  - 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.
PG  - 99-111
LID - 10.37349/emed.2022.00077 [doi]
AB  - 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-alpha), 
      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. Aim: Our goal was to determine if PE CD4(+) T cells 
      stimulate AT1-AA in pregnant nude-athymic rats. 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 MAP [114 +/- 1 mmHg (n = 
      9)] and AT1-AA [19.8 +/- 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 +/- 2 mmHg (n 
      = 7, P < 0.05) and 1.3 +/- 0.9 bpm (n = 5, P < 0.05)]. Rituximab (103 +/- 2 mmHg, n = 
      3, P < 0.05) and anti-CD40L (102 +/- 1 mmHg, n = 3, P < 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. 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.
FAU - Reeve, Kristin E
AU  - Reeve KE
AD  - Department of Obstetrics and Gynecology, University of Mississippi Medical 
      Center, Jackson, MS 39216, USA.
FAU - Deer, Evangeline
AU  - Deer E
AD  - Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 
      39216, USA.
FAU - Amaral, Lorena M
AU  - Amaral LM
AD  - Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 
      39216, USA.
FAU - Cornelius, Denise C
AU  - Cornelius DC
AD  - Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 
      39216, USA.
AD  - Department of Emergency Medicine, University of Mississippi Medical Center, 
      Jackson, MS 39216, USA.
FAU - Herrock, Owen
AU  - Herrock O
AD  - Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 
      39216, USA.
FAU - Harmon, Ashlyn C
AU  - Harmon AC
AD  - Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 
      39216, USA.
FAU - Campbell, Nathan
AU  - Campbell N
AD  - Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 
      39216, USA.
FAU - Fitzgerald, Sarah
AU  - Fitzgerald S
AD  - Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 
      39216, USA.
FAU - Ibrahim, Tarek
AU  - Ibrahim T
AD  - Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 
      39216, USA.
FAU - Wallukat, Gerd
AU  - Wallukat G
AD  - Experimental and Clinical Research Center, Max-Delbruck-Centrum fur Molekulare 
      Medizin, 13092 Berlin, Germany.
FAU - Dechend, Ralf
AU  - Dechend R
AD  - Experimental and Clinical Research Center, Max-Delbruck-Centrum fur Molekulare 
      Medizin, 13092 Berlin, Germany.
FAU - LaMarca, Babbette
AU  - LaMarca B
AD  - Department of Pharmacology, University of Mississippi Medical Center, Jackson, MS 
      39216, USA.
LA  - eng
GR  - R01 HD067541/HD/NICHD NIH HHS/United States
GR  - P20 GM121334/GM/NIGMS NIH HHS/United States
GR  - U54 GM115428/GM/NIGMS NIH HHS/United States
GR  - R01 HL151407/HL/NHLBI NIH HHS/United States
GR  - T32 HL105324/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20220225
PL  - United States
TA  - Explor Med
JT  - Exploration of medicine
JID - 101765387
PMC - PMC10465114
MID - NIHMS1875586
OTO - NOTNLM
OT  - Adaptive immunity
OT  - CD4+ T cells
OT  - hypertensions
OT  - pre-eclampsia
COIS- Conflicts of interest The authors declare they have no conflict of interest.
EDAT- 2022/01/01 00:00
MHDA- 2022/01/01 00:01
PMCR- 2023/08/29
CRDT- 2023/08/30 03:50
PHST- 2022/01/01 00:01 [medline]
PHST- 2022/01/01 00:00 [pubmed]
PHST- 2023/08/30 03:50 [entrez]
PHST- 2023/08/29 00:00 [pmc-release]
AID - 10.37349/emed.2022.00077 [doi]
PST - ppublish
SO  - Explor Med. 2022;3(1):99-111. doi: 10.37349/emed.2022.00077. Epub 2022 Feb 25.