Activation of T-lymphocytes and herpes viruses in atherosclerotic plaques

Abstract

Aim: In our previous work we found that T-lymphocytes phenotypes in atherosclerotic plaques are different from those found in blood. T cells are more activated in plaque than in blood as judged by the expression of CD25, CD38, and HLA-DR. The purpose of this work was to evaluate the presence of herpesviruses (HHV) in these plaques and investigate whether their presence correlates with activation of resident lymphocytes. Methods: 27 atherosclerotic plaques from patients who underwent either carotid endarterectomy (22) or aortofemoral bypass grafting (5). The degree of carotid artery stenosis varied from 70% to 90% (median 80.0%, IQR 72.5–90). The phenotype of lymphocytes was analyzed using polychromatic flow cytometry, and HHVs DNA amount in plaques was measured by Real Time PCR. Results: We found a correlation between T lymphocytes activation and the presence of certain HHVs in atherosclerotic plaques. The fraction of CD4+ T cells expressing the late activation marker HLA-DR positively correlates with HHV-1 & -2 viral load (Spearman's r=0.438, p=0.0381). Also, there was a negative correlation between the fraction of naive CD8 T cells and HHV-7 viral load (Spearman's r= -0.7381, p=0.0366). And the viral load of HHV-4 correlated with the presence of late-differentiated effector memory CD4 T cells (Spearman's r=0.6364, p=0.0353) and effector memory CD8 T cells (Spearman's r=0.6636, p=0.026). Conclusions: The activation of T-lymphocytes in atherosclerotic plaque is correlated with the presence of different HHV types (1, 4 and 7). The presence of HHVs in atherosclerotic plaques may be an important factor of lymphocyte activation thus affecting plaques' maturation and rupture. This is the first study, which quantitatively associates activation of atherosclerotic plaques' resident lymphocytes with the presence of certain HHVs in theses plaques. The finding of this association may lead to the development of new targets for atherosclerosis preventive therapy and warrants further investigation.