ArticleHypertension (Dallas, Tex. : 1979)2015
Regulatory T cells ameliorate intrauterine growth retardation in a transgenic rat model for preeclampsia.
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Article in Hypertension (Dallas, Tex. : 1979), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15citing papers in PubMed
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Who cites it
15 citing papers in PubMed, 38 citations in OpenAlex.
- Regulatory T cells in human pregnancy: mechanisms, dysregulation, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Prenatal inflammation exacerbates hyperoxia-induced neonatal brain injury.Journal of neuroinflammation · 2025Article
- A comprehensive review of the roles of T-cell immunity in preeclampsia.Frontiers in immunology · 2025Review
- Cellular immune responses in the pathophysiology of preeclampsia.Journal of leukocyte biology · 2022Review
- Vagus nerve stimulation ameliorates L-NAME-induced preeclampsia-like symptoms in rats through inhibition of the inflammatory response.BMC pregnancy and childbirth · 2021Article
- Deficiency in CD4 T Cells Leads to Enhanced Postpartum Internal Carotid Artery Vasoconstriction in Mice: The Role of Nitric Oxide.Frontiers in physiology · 2021Article
- RNA interference therapeutics targeting angiotensinogen ameliorate preeclamptic phenotype in rodent models.The Journal of clinical investigation · 2020Article
- Dysfunction of Tregs contributes to FGR pathogenesis via regulating Smads signalling pathway.Journal of cellular and molecular medicine · 2020Article
- Therapeutic Potential of Regulatory T Cells in Preeclampsia-Opportunities and Challenges.Frontiers in immunology · 2019Review
- Developmental origins of nonalcoholic fatty liver disease as a risk factor for exaggerated metabolic and cardiovascular-renal disease.American journal of physiology. Endocrinology and metabolism · 2018Review
- Regulatory T cells in embryo implantation and the immune response to pregnancy.The Journal of clinical investigation · 2018Review
- Proliferation of endogenous regulatory T cells improve the pathophysiology associated with placental ischaemia of pregnancy.American journal of reproductive immunology (New York, N.Y. : 1989) · 2017Article
- Impact of Immune Deficiency on Remodeling of Maternal Resistance Vasculature 4 Weeks Postpartum in Mice.Reproductive sciences (Thousand Oaks, Calif.) · 2017Article
- Preeclampsia and health risks later in life: an immunological link.Seminars in immunopathology · 2016Review
- Preeclampsia and Pregnancy-Related Hypertensive Disorders.Hypertension (Dallas, Tex. : 1979) · 2016Review
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Authors and funding
16 authors at 2 institutions in 2 countries.
Lukasz PrzybylFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Tarek IbrahimFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Nadine HaaseFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Michaela GolicFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Julianna RugorFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Friedrich C LuftFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Ivo BendixFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Meray SerdarFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Gerd WallukatFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Anne Cathrine StaffFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Dominik N MüllerFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Thomas HünigFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Ursula Felderhoff-MüserFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Florian HerseFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Babette LaMarcaFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.).
Ralf DechendFrom the Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany (L.P., N.H., M.G., J.R., F.C.L., G.W., D.N.M., F.H., R.D.); Department of Pharmacology/Toxicology, Center for Excellence in Cardiovascular and Renal Research, Jackson, MS (T.I., B.L.); Department of Pediatrics I, Neonatal Neuroscience Lab, University Hospital Essen, University Duisburg-Essen, Essen, Germany (I.B., M.S., U.F.-M.); Departments of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway (A.C.S.); Institute of Virology and Immunobiology, Würzburg, Germany (T.H.); and Department of Cardiology and Nephrology, HELIOS-Klinikum, Berlin, Germany (R.D.). ralf.dechend@charite.de.
Center for Excellence in Education · USOslo University Hospital · NO
Funding
The Kidney, Hypertension, Pregnancy and InflammationR01HD067541 · NICHD · UNIVERSITY OF MISSISSIPPI MED CTR · PI LAMARCA, BABBETTE · 2011 to 2020
$3.1MNICHD NIH HHS R01 HD067541
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.
Indexed as
Pregnancy, AnimalAnimalsAntibodies, MonoclonalCD28 AntigensDisease Models, AnimalFemaleFetal Growth RetardationLymphocyte ActivationPre-EclampsiaPregnancyPregnancy OutcomeRandom AllocationRatsRats, TransgenicT-Lymphocytes, RegulatoryAntibodies, MonoclonalCD28 Antigensfetal growth retardationpreeclampsiapregnancyT-lymphocytes, regulatory
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