key: cord-0837261-zrmqoqv0 authors: Zhang, Chao; Wang, Fu-Sheng; Silvestre, Jean-Sébastien; Arenzana-Seisdedos, Fernando; Tang, Hong title: Is aberrant CD8+ T cell activation by hypertension associated with cardiac injury in severe cases of COVID-19? date: 2020-05-12 journal: Cell Mol Immunol DOI: 10.1038/s41423-020-0454-3 sha: b48ecc6f18f7b229fba72e0b54f967a5bc0baa42 doc_id: 837261 cord_uid: zrmqoqv0 nan end-organ damage are in part mediated by activation of these infiltrated cells. 18 Our lab showed that mice lacking CD8+ T cells are efficiently protected from hypertension-induced cardiac damage. CD8+ T cells thus can sense the hypertension independent of T cell receptor. 19 More importantly, CD8+ T cells are required for macrophage infiltration in myocardium and subsequent activation by CD8+ T cells secreted IFN-γ. How do CD8+ T cells respond to hypertension? One study suggests that mineralocorticoid receptor on CD8+ T cells directly sense blood pressure and promote inflammatory milieu through secreting IFN-γ. 20, 21 Furthermore, hypertension can trigger oxidative modification of proteins in DC cells by highly reactive γ-ketoaldehydes (isoketals), which activate DC to produce IL-6, IL-1β, and IL-23. Activated DCs promote T cell, particularly CD8+ T cell, proliferation and production of IFN-γ and IL-17A. 22 Intriguingly, a secondary hemophagocytic lymphohistiocytosis, which associates with a massive CD8+ T cell and macrophage activation but decreased NK cell activity, has been noted for COVID-19 patients in European ICUs. Taken together, these results suggest that CD8+ T cells may function as a key hypertension effector that drives macrophage-mediated cardiac damage. Severe COVID-19 patients also showed increased IL-6, IL-1β, and IFN-γ. 23 It is worthy of studying whether blockade of IL-6 or IL-1β, which is currently under clinical trials, would reduce cardiac injury through inhibition of CD8 + T cell-macrophage infiltration and overactivation. The glucocorticoid treatment of ICU patients shall also be closely monitored for potential beneficial or detrimental effect on CD8 + T cell activation. Lastly, CCR5 is a major chemoattracting receptor in CD8 + T cells that involves in various pathogenic conditions, including viral infections. 24 The antiviral drugs, such as Selzentry (maraviroc) and Leronlimab (PRO 140), have been successfully used for treatment of AIDS. 25 It is therefore of great interest to study whether these drugs can block cardiac infiltration of CD8 + T cells thereby reduce hypertensive cardiac injury of COVID-19 patients. Competing interests: The authors declare no competing interests. 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