Virus specific CD8+ T-cells accumulate, but do not recognize antigen, in the atherosclerotic lesion. (10th June 2022) - De Jong, M
Abstract: Funding Acknowledgements: Type of funding sources: Public grant(s) – EU funding. Main funding source(s): ERA CVD Dutch Heart Foundation Viral infections have been associated with the progression of atherosclerosis. CD8+ T-cells directed against common viruses, such as influenza and Epstein-Barr virus, have been detected inside of human atherosclerotic lesions. These virus specific CD8+ T-cells have been hypothesized to contribute to the development of atherosclerosis, however, their mechanism of action in the atherosclerotic lesion remains unclear. This study aimed to characterize the behavior of virus specific CD8+ T-cells in the atherosclerotic lesion. The presence of virus specific CD8+ T-cells in atherosclerotic lesions was assessed by performing T-cell receptor (TCR)-β sequencing on human endarterectomy samples and patient matched blood samples (N=10). These TCRs were subsequently compared to known virus specific TCR sequences. Virus specific CD8+ T-cells seemed to accumulate in the atherosclerotic lesion (mean=3.5%), compared to patient matched blood samples (mean=2.0%) (p=0.053). Moreover, these virus specific CD8+ T-cells produced significantly more IFN-γ (p=0.0009) and Granzyme B (p=0.0038) in response to external stimuli, suggesting these T-cells may play a pro-inflammatory role in the pathogenesis of atherosclerosis. To investigate if virus specific CD8+ T-cells can be stimulated in situ, the immunopeptidome of 51 pooled human plaques was determined and matched with various viral peptidomes. Only one peptide presented in the atherosclerotic lesions matched a viral peptidome, rendering almost all virus specific CD8+ T-cells in the lesion antigen non-specific. In conclusion, virus specific CD8+ T-cells are enriched in atherosclerotic lesions and have an activated phenotype, compared to other plaque residing CD8+ T-cells. The absence of virus specific antigen presentation in the atherosclerotic lesion suggests that if these CD8+ T-cells contribute to inflammation, they do so in an antigen independent manner.