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Regulatory T cells ameliorate intrauterine growth retardation in a transgenic rat model for preeclampsia

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Item Type:Article
Title:Regulatory T cells ameliorate intrauterine growth retardation in a transgenic rat model for preeclampsia
Creators Name:Przybyl, L. and Ibrahim, T. and Haase, N. and Golic, M. and Rugor, J. and Luft, F.C. and Bendix, I. and Serdar, M. and Wallukat, G. and Staff, A.C. and Müller, D.N. and Hünig, T. and Felderhoff-Müser, U. and Herse, F. and LaMarca, B. and Dechend, R.
Abstract:Preeclampsia is a multisystemic syndrome during pregnancy that is often associated with intrauterine growth retardation. Immunologic dysregulation, involving T cells, is implicated in the pathogenesis. The aim of this study was to evaluate the effect of upregulating regulatory T cells in an established transgenic rat model for preeclampsia. Application of superagonistic monoclonal antibody for CD28 has been shown to effectively upregulate regulatory T cells. In the first protocol (treatment protocol), we applied 1 mg of CD28 superagonist or control antibody on days 11 and 15 of pregnancy. In the second protocol (prevention protocol), the superagonist or control antibody was applied on days 1, 5, and 9. Superagonist increased regulatory T cells in circulation and placenta from 8.49+/-2.09% of CD4-positive T cells to 23.50+/-3.05% and from 3.85+/-1.45% to 23.27+/-7.64%, respectively. Blood pressure and albuminuria (30.6+/-15.1 versus 14.6+/-5.5 mg/d) were similar in the superagonist or control antibody-treated preeclamptic group for both protocols. Rats treated with CD28 superagonist showed increased pup weights in the prevention protocol (2.66+/-0.03 versus 2.37+/-0.05 g) and in the treatment protocol (3.04+/-0.04 versus 2.54+/-0.1 g). Intrauterine growth retardation, calculated by brain:liver weight ratio, was also decreased by the superagonist in both protocols. Further analysis of brain development revealed a 20% increase in brain volume by the superagonist. Induction of regulatory T cells in the circulation and the uteroplacental unit in an established preeclamptic rat model had no influence on maternal hypertension and proteinuria. However, it substantially improved fetal outcome by ameliorating intrauterine growth retardation.
Keywords:Fetal Growth Retardation, Preeclampsia, Pregnancy, Regulatory T-Lymphocytes
Publisher:American Heart Association
Page Range:1298-1306
Date:June 2015
Additional Information:Copyright © 2015 American Heart Association, Inc.
Official Publication:https://doi.org/10.1161/HYPERTENSIONAHA.114.04892
PubMed:View item in PubMed

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