Impaired CD4+ T cell response to apolipoprotein B-100 peptide P210 in atherosclerotic cardiovascular disease is reversed by P210-conjugated nanoparticles.

The apolipoprotein B-100 (ApoB-100) peptide P210 (amino acids 3136-3155) is localized within atherosclerotic plaques, and low IgG autoantibody levels against P210 are associated with a higher risk of plaque rupture and myocardial infarction (MI), suggesting that this humoral immunity is protective in atherosclerotic cardiovascular disease (ASCVD). While the clinical significance of P210 antibody response has been shown, it remains unclear whether ASCVD patients also exhibit an impaired T cell response to P210. Thus, we investigated the T cell response to P210 in ASCVD patients and evaluated its potential as a target for therapeutic intervention. Peripheral blood mononuclear cells (PBMCs) collected from ASCVD patients and controls were stimulated with the P210 peptide and evaluated for T cell responses using the Activated Immune Markers (AIM) assay. PBMC from ASCVD patients stimulated with P210 had significantly impaired CD4+CD69+CD154+ T cell response which persisted into follow-up a year later. Significantly reduced CD4+ T follicular helper cell responses to P210 were also noted in ASCVD patients. Given the beneficial immunomodulation by P210 nanoparticles (P210-PAM) that resulted in reduced atherosclerosis in mice, we investigated its effect on PBMCs from ASCVD patients. Treatment with P210-PAM significantly improved the impaired CD4+CD69+CD154+ and CD4+CD134+CD137+ T cell activation in response to P210. The study suggests potential future clinical translation for P210-PAM as an immune-modulation strategy for ASCVD.