Low-Density Lipoprotein-Reactive T Cells Regulate Plasma Cholesterol Levels and Development of Atherosclerosis in Humanized Hypercholesterolemic Mice
(2018) In Circulation 138(22). p.2513-2526- Abstract
- Background: Atherosclerotic cardiovascular disease is a chronic inflammatory process initiated when cholesterol-carrying low-density lipoprotein (LDL) is retained in the arterial wall. CD4+ T cells, some of which recognize peptide components of LDL as antigen, are recruited to the forming lesion, resulting in T-cell activation. Although these T cells are thought to be proatherogenic, LDL immunization reduces disease in experimental animals. These seemingly contradictory findings have hampered the development of immune-based cardiovascular therapy. The present study was designed to clarify how activation of LDL-reactive T cells impacts on metabolism and vascular pathobiology.
Methods: We have developed a T-cell receptor-transgenic... (More) - Background: Atherosclerotic cardiovascular disease is a chronic inflammatory process initiated when cholesterol-carrying low-density lipoprotein (LDL) is retained in the arterial wall. CD4+ T cells, some of which recognize peptide components of LDL as antigen, are recruited to the forming lesion, resulting in T-cell activation. Although these T cells are thought to be proatherogenic, LDL immunization reduces disease in experimental animals. These seemingly contradictory findings have hampered the development of immune-based cardiovascular therapy. The present study was designed to clarify how activation of LDL-reactive T cells impacts on metabolism and vascular pathobiology.
Methods: We have developed a T-cell receptor-transgenic mouse model to characterize the effects of immune reactions against LDL. Through adoptive cell transfers and cross-breeding to hypercholesterolemic mice expressing the antigenic human LDL protein apolipoprotein B-100, we evaluate the effects on atherosclerosis.
Results: A subpopulation of LDL-reactive T cells survived clonal selection in the thymus, developed into T follicular helper cells in lymphoid tissues on antigen recognition, and promoted B-cell activation. This led to production of anti-LDL immunoglobulin G antibodies that enhanced LDL clearance through immune complex formation. Furthermore, the cellular immune response to LDL was associated with increased cholesterol excretion in feces and with reduced vascular inflammation. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/74a48fc6-8382-46ea-bd39-30ffd3d3861c
- author
- Gisterå, Anton ; Klement, Maria LU ; Polyzos, Konstantinos A. ; Mailer, Reiner K.W. ; Duhlin, Amanda ; Karlsson, Mikael C.I. ; Ketelhuth, Daniel F. J. and Hansson, Göran K
- organization
- publishing date
- 2018-11-27
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Circulation
- volume
- 138
- issue
- 22
- pages
- 2513 - 2526
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- scopus:85050694005
- ISSN
- 1524-4539
- DOI
- 10.1161/CIRCULATIONAHA.118.034076
- language
- English
- LU publication?
- yes
- id
- 74a48fc6-8382-46ea-bd39-30ffd3d3861c
- date added to LUP
- 2026-05-06 11:01:13
- date last changed
- 2026-05-08 13:07:23
@article{74a48fc6-8382-46ea-bd39-30ffd3d3861c,
abstract = {{Background: Atherosclerotic cardiovascular disease is a chronic inflammatory process initiated when cholesterol-carrying low-density lipoprotein (LDL) is retained in the arterial wall. CD4+ T cells, some of which recognize peptide components of LDL as antigen, are recruited to the forming lesion, resulting in T-cell activation. Although these T cells are thought to be proatherogenic, LDL immunization reduces disease in experimental animals. These seemingly contradictory findings have hampered the development of immune-based cardiovascular therapy. The present study was designed to clarify how activation of LDL-reactive T cells impacts on metabolism and vascular pathobiology.<br/><br/>Methods: We have developed a T-cell receptor-transgenic mouse model to characterize the effects of immune reactions against LDL. Through adoptive cell transfers and cross-breeding to hypercholesterolemic mice expressing the antigenic human LDL protein apolipoprotein B-100, we evaluate the effects on atherosclerosis.<br/><br/>Results: A subpopulation of LDL-reactive T cells survived clonal selection in the thymus, developed into T follicular helper cells in lymphoid tissues on antigen recognition, and promoted B-cell activation. This led to production of anti-LDL immunoglobulin G antibodies that enhanced LDL clearance through immune complex formation. Furthermore, the cellular immune response to LDL was associated with increased cholesterol excretion in feces and with reduced vascular inflammation.}},
author = {{Gisterå, Anton and Klement, Maria and Polyzos, Konstantinos A. and Mailer, Reiner K.W. and Duhlin, Amanda and Karlsson, Mikael C.I. and Ketelhuth, Daniel F. J. and Hansson, Göran K}},
issn = {{1524-4539}},
language = {{eng}},
month = {{11}},
number = {{22}},
pages = {{2513--2526}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Circulation}},
title = {{Low-Density Lipoprotein-Reactive T Cells Regulate Plasma Cholesterol Levels and Development of Atherosclerosis in Humanized Hypercholesterolemic Mice}},
url = {{http://dx.doi.org/10.1161/CIRCULATIONAHA.118.034076}},
doi = {{10.1161/CIRCULATIONAHA.118.034076}},
volume = {{138}},
year = {{2018}},
}