Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice.
X Zhou, … , S Stemme, G K Hansson
X Zhou, … , S Stemme, G K Hansson
Published April 15, 1998
Citation Information: J Clin Invest. 1998;101(8):1717-1725. https://doi.org/10.1172/JCI1216.
View: Text | PDF
Research Article Article has an altmetric score of 6

Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice.

  • Text
  • PDF
Abstract

Atherosclerosis is an inflammatory-fibrotic response to accumulation of cholesterol in the artery wall. In hypercholesterolemia, low density lipoproteins (LDL) accumulate and are oxidized to proinflammatory compounds in the arterial intima, leading to activation of endothelial cells, macrophages, and T lymphocytes. We have studied immune cell activation and the autoimmune response to oxidized LDL in atherosclerotic apo E-knockout mice. Autoantibodies to oxidized LDL exhibited subclass specificities indicative of T cell help, and the increase in antibody titers in peripheral blood was associated with increased numbers of cytokine-expressing T cells in the spleen. In addition to T cell-dependent antibodies, IgM antibodies to oxidized LDL were also increased in apo E-knockout mice. This suggests that both T cell-dependent and T cell-independent epitopes may be present on oxidized LDL. In moderate hypercholesterolemia, IgG antibodies were largely of the IgG2a isotype, suggesting that T cell help was provided by proinflammatory T helper (Th) 1 cells, which are prominent components of atherosclerotic lesions. In severe hypercholesterolemia induced by cholesterol feeding of apo E-knockout mice, a switch to Th2-dependent help was evident. It was associated with a loss of IFN-gamma-producing Th1 cells in the spleen, whereas IL-4-producing Th2 cells were more resistant to hypercholesterolemia. IFN-gamma but not IL-4 mRNA was detected in atherosclerotic lesions of moderately hypercholesterolemic apo E-knockout mice, but IL-4 mRNA appeared in the lesions when mice were made severely hypercholesterolemic by cholesterol feeding. These data show that IFN-gamma-producing Th1 cells infiltrate atherosclerotic lesions and provide T cell help for autoimmune responses to oxidized LDL in apo E-knockout mice. However, severe hypercholesterolemia is associated with a switch from Th1 to Th2, which results not only in the formation of IgG1 autoantibodies to oxidized LDL, but also in the appearance of Th2-type cytokines in the atherosclerotic lesions. Since the two subsets of T cells counteract each other, this switch may have important consequences for the inflammatory/immune process in atherosclerosis.

Authors

X Zhou, G Paulsson, S Stemme, G K Hansson

×

Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1990 Total
Citations: 3 3 3 5 10 8 7 5 6 13 12 15 7 15 15 8 15 15 15 18 17 12 18 23 21 14 2 1 306
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2020 (10)

Title and authors Publication Year
Maternal exposure to soy diet reduces atheroma in hyperlipidemic F1 offspring mice by promoting macrophage and T cell anti-inflammatory responses
RL Burris, SC Vick, B Popovic, PE Fraungruber, S Nagarajan
Atherosclerosis 2020
Autoantibody Responses to Apolipoprotein A-I Are Not Diet- or Sex-Linked in C57BL/6 Mice
MG Pitts, D Nardo, CM Isom, VJ Venditto
ImmunoHorizons 2020
Meta-Analysis of Leukocyte Diversity in Atherosclerotic Mouse Aortas
A Zernecke, H Winkels, C Cochain, JW Williams, D Wolf, O Soehnlein, CS Robbins, C Monaco, I Park, CA McNamara, CJ Binder, MI Cybulsky, CA Scipione, CC Hedrick, EV Galkina, T Kyaw, Y Ghosheh, HQ Dinh, K Ley
Circulation research 2020
T cell co-stimulator inducible co-stimulatory (ICOS) exerts potential anti-atherosclerotic roles through downregulation of vascular smooth muscle phagocytosis and proliferation
Z Zhong, Q Zhang, L Tan, X Guo, C Gan
Annals of translational medicine 2020
atherosclerosis: gone with the Wnt?
P Boucher, RL Matz, J Terrand
Atherosclerosis 2020
Sex as a Determinant of Responses to a Coronary Artery Disease Self-Antigen Identified by Immune-Peptidomics
WM Lio, B Cercek, J Yano, W Yang, J Ghermezi, X Zhao, J Zhou, B Zhou, MR Freeman, KY Chyu, PK Shah, PC Dimayuga
Frontiers in immunology 2020
Association between Dyslipidemia and Chronic Rhinosinusitis in a Korean Population
JH Wee, C Min, MW Park, SH Byun, HJ Lee, CM Song, B Park, HG Choi
Diagnostics 2020
Interactive effects of interferon-gamma functional single nucleotid polymorphism (+874 T/A) with cardiovascular risk factors in coronary heart disease and early myocardial infarction risk
AB Akadam-Teker, E Teker, A Daglar-Aday, KC Pekkoc-Uyanik, EI Aslan, Ö Kucukhuseyin, G Ozkara, H Yılmaz-Aydoğan
Molecular Biology Reports 2020
Suppression of microRNA-155 exerts an anti-inflammatory effect on CD4+ T cell-mediated inflammatory response in the pathogenesis of atherosclerosis
J Zheng, W Wang, T Hong, S Yang, J Shen, C Liu
Acta Biochimica et Biophysica Sinica 2020
The Effects of Aronia melanocarpa Juice Consumption on the mRNA Expression Profile in Peripheral Blood Mononuclear Cells in Subjects at Cardiovascular Risk
L Stojković, I Jovanović, M Zivković, M Zec, T Djurić, I Zivotić, J Kuveljić, A Kolaković, I Kolić, A Djordjević, M Glibetić, D Alavantić, A Stanković
Nutrients 2020

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 8 patents
106 readers on Mendeley
See more details