Low density lipoprotein promotes human naive T cell differentiation to Th1 cells.
Oxidized LDL (oxLDL) in the arterial wall and its incorporation into foam cells leads to inflammation and nucleation of atherosclerotic plaque; this is opposed by HDL. OxLDL and HDL regulate activation of macrophages and endothelial cells, and study of T cell participation has been limited to mature, differentiated cells such as Th1 cells, which perpetuate atherogenesis by promoting cell-mediated responses and inflammation. Immature naïve T cells, just emerged from the thymus, have remained largely unstudied. We hypothesized that LDL and HDL provide selective modulation of immature naïve T cell differentiation and participation in plaque development. In our in vitro model, naïve cells become activated and differentiate to mature effector T cells that are Th1, Th2 or Treg cells. Addition of oxLDL favored differentiation to Th1 cells, reduced Th2 cell activity and prolonged cell survival. In contrast, HDL inhibited T cell proliferation and reduced cell survival. The data suggest a novel mechanism where oxLDL enhances differentiation of human naïve CD4+ T cells to Th1 cells capable of promoting inflammation and plaque progression, and this is opposed by HDL.
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, United States.
Amy H
AH
Newton
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, United States. Electronic address: sbene@ku.edu.
Stephen H
SH
Benedict
D000328:Adult; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D015415:Biomarkers; D018106:CD28 Antigens; D017252:CD3 Complex; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1
Atherosclerosis; Human naïve T cells; LDL; T cell differentiation; Th1 cells