@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}},
}