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 naive T cells, just emerged from the thymus, have remained largely unstudied. We hypothesized that LDL and HDL provide selective modulation of immature naive T cell differentiation and participation in plaque development. In our in vitro model, naive 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 naive CD4+ T cells to Th1 cells capable of promoting inflammation and plaque progression, and this is opposed by HDL. (C) 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.