Cytomegalovirus (CMV) infection is a major driver of accelerated immunosenescence related to CD28null T cells expansion. CMV infection and these proatherogenic T cells have been independently associated with cardiovascular disease and COVID-19 severity. We have investigated the potential contribution of SARS-CoV-2 to immunosenescence and its relationship with CMV.Innate and adaptive immune subpopulations from mild/asymptomatic SARS-CoV-2 infected (mCOVID-19) individuals, and healthy donors (HD) were immunophenotyped. A significant increase of CD28nullCD57 + CX3CR1+ T cell percentages (CD4+ (P ≤ 0.01), CD8+ (P ≤ 0.01) and TcRγδ (CD4−CD8-) (P ≤ 0.001)) was found in mCOVID-19 CMV + individuals stable up to 12 months post-infection. This expansion did not occur in mCOVID-19 CMV- individuals or in CMV + individuals that were infected post SARS-CoV-2 vaccination (vmCOVID-19). Moreover, mCOVID-19 individuals showed no significant differences with aortic stenosis patients. Thus, individuals coinfected with SARS-CoV-2 and CMV suffer accelerated T cell senescence, which might ultimately lead to an increased risk of cardiovascular disease.
Aortic stenosis (AS) is a frequent cardiac disease in old individuals, characterized by valvular calcification, fibrosis, and inflammation. Recent studies suggest that AS is an active inflammatory atherosclerotic-like process. Particularly, it has been suggested that several immune cell types, present in the valve infiltrate, contribute to its degeneration and to the progression toward stenosis. Furthermore, the infiltrating T cell subpopulations mainly consist of oligoclonal expansions, probably specific for persistent antigens. Thus, the characterization of the cells implicated in the aortic valve calcification and the analysis of the antigens to which those cells respond to is of utmost importance to develop new therapies alternative to the replacement of the valve itself. However, calcified aortic valves have been only studied so far by histological and immunohistochemical methods, unable to render an in-depth phenotypical and functional cell profiling. Here we present, for the first time, a simple and efficient cytometry-based protocol that allows the identification and quantification of infiltrating inflammatory leukocytes in aortic valve explants. Our cytometry protocol saves time and facilitates the simultaneous analysis of numerous surface and intracellular cell markers and may well be also applied to the study of other cardiac diseases with an inflammatory component.
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