Antigen-Specific Cd8+ T-Cells Are Involved In Human Carotid Atherosclerotic Plaques Destabilization

Immunization of ApoE-/- mice expressing human HLA-A 02:01 with p210, an apoB100-derived peptide, reduces atherosclerotic plaque development by inducing a p210-specific CD8+ T cell population. Studying Class-I MHC/CD8+ T cell signaling offers a promising approach to understanding the mechanism behind the athero-protective effects of p210 immunization. We aimed to identify a p210-specific CD8+ T cell population in human carotid atherosclerotic plaques from blood-positive HLA-A 02:01 patients undergoing surgical carotid endarterectomy (CEA). The study included 22 consecutive patients who were HLA-A 02:01 (+) out of 49 enrolled (reflecting an estimated prevalence of about 30% HLA-A02:01(+) in the Caucasian population). Immunohistochemistry staining used a PE-marked A 02:01-KTTKQSFDL Pentamer on fixed endarterectomy plaques. Both HLA-A 02:01 (+) and (-) patient plaques were used, with the latter serving as an internal negative control. Presence of pentamer (+) CD8 T cells indicated a p210-specific CD8+ T cell population. Patients positive for HLA-A 02:01 showed an average of 3.40 {+/-} 2.17 x 10^3 HPF p210-specific CD8+ T cells (61.80%, 3% of total CD3+) in the shoulders of atherosclerotic plaques post-CEA, significantly higher than in controls (p < 0.0001). The proportion of p210-specific CD8+ T cells was lower in plaques displaying morphological features of instability. This study, for the first time, identifies a p210-specific CD8+ T cell population in human carotid atherosclerotic plaques from HLA-A02:01(+) patients, suggesting a role for autoimmunity in atherosclerosis development and supporting the potential efficacy of p210 immunization in HLA-A02:01 (+) individuals to reduce atherosclerosis. The variation in this specific T cell population within human plaques correlates with plaque vulnerability, highlighting p210-specific CD8+ T cells as a potential target for future therapies.