Apolipoprotein B-100 Peptide p210 Inhibits Proliferation of Na?ve T Effector Cells and Promotes Induction of Tolerogenic Antigen Presenting Cells and Regulatory T Cells in Vitro

Abstract

Objectives: Modulation of immune responses against LDL antigens through therapeutic vaccines represents a possible new approach for prevention of cardiovascular disease. The mode of action of these vaccines remains to be fully characterized but the protective effect of immunization with the apolipoprotein B-100 (apoB-100) derived peptide p210 has in several studies been associated with activation of regulatory T cells. The present study used an in vitro model to study the effect of p210 on immune cells. Methods and results: CD11c + antigen presenting cells, CD25 -CD4 + naïve T effector cells and CD25 + CD4 + T regulatory cells were isolated from mouse spleens using antibody-coated magnetic beads. Pre-incubation of antigen presenting cells with p210 conjugated to cationized bovine serum albumin (p210-cBSA) down-regulated the expression of CD86 and MHC class II molecules, inhibited proliferation of pre-activated naïve T effector cells and stimulated conversion of these cells into regulatory T cells. These effects were shown to partly be mediated through a suppression of the release of IL-12 from antigen presenting cells. Conclusions: The present findings demonstrate that p210-cBSA inhibits proliferation of naïve T effector cells and promotes their conversion into regulatory T cells and this is suggested to be associated with a reduced activation status of antigen presenting cells. Taken together these findings suggest that immunization with p210-based vaccines have the capability of inducing tolerogenic APCs that in turn generate regulatory T cells suppressing T effector cell functions.