ApoB-specific CD4+ T cells circulate in human blood and formation of a memory population is driven by coronary artery disease and an elevated cardiovascular risk profile

Abstract Aim Atherosclerosis is a chronic inflammatory disease involving an autoimmune response against Apolioprotein B (ApoB), the core protein of low-density lipoprotein (LDL) cholesterol. Using a translational bench-to-bedside approach, we linked the presence and immuno-phenotype of ApoB-specific CD4+ T cells to clinical risk profiles for cardiovascular disease in humans. Methods Peripheral blood mononuclear cells (PBMCs) from 230 patients that underwent coronary angiography were co-incubated in vitro with a pool of immunodominant peptides from human ApoB for 6h. Reactive ApoB-specific T cells (ApoB+) were defined in flow cytometry by expression of the activation marker CD40L. Partition of ApoBpos into naïve and memory T cells was achieved by extracellular fluorochrome-based staining of CD45RO, CCR7 and CD45RA. Cytokine expression of ApoBpos was determined by intracellular staining. Results We found that a median of 0.69±0.1% of circulating CD4+ T cells were reactive to Apolipoprotein B. We found detectable concentrations of auto reactive ApoB+ T cells in 86,44% of all healthy individuals. However, overall frequencies of ApoB reactive T cells did not correlate with diagnosed coronary artery disease (CAD). Compared to ApoBneg. T cells, we detected a higher fraction of memory T cells in ApoBpos (p