Tomić, Sergej (36057468900)Sergej (36057468900)TomićĐokić, Jelena (57222324574)Jelena (57222324574)ĐokićStevanović, Dejan (57461284600)Dejan (57461284600)StevanovićIlić, Nataša (7006245468)Nataša (7006245468)IlićGruden-Movsesijan, Alisa (6507165225)Alisa (6507165225)Gruden-MovsesijanDinić, Miroslav (57191052264)Miroslav (57191052264)DinićRadojević, Dušan (57219611119)Dušan (57219611119)RadojevićBekić, Marina (57204740290)Marina (57204740290)BekićMitrović, Nebojša (56235199600)Nebojša (56235199600)MitrovićTomašević, Ratko (6603547250)Ratko (6603547250)TomaševićMikić, Dragan (7003675540)Dragan (7003675540)MikićStojanović, Dragoš (7007127826)Dragoš (7007127826)StojanovićČolić, Miodrag (20933591700)Miodrag (20933591700)Čolić2025-06-122025-06-122021https://doi.org/10.3389/fimmu.2021.614599https://www.scopus.com/inward/record.uri?eid=2-s2.0-85102247023&doi=10.3389%2ffimmu.2021.614599&partnerID=40&md5=52e451ec59ea6da9ae94e5c399b7a2dahttps://remedy.med.bg.ac.rs/handle/123456789/4270Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed ~140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with ~30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-γ production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease. © Copyright © 2021 Tomić, Đokić, Stevanović, Ilić, Gruden-Movsesijan, Dinić, Radojević, Bekić, Mitrović, Tomašević, Mikić, Stojanović and Čolić.autophagyCOVID-19cytokinesmyeloid-derived suppressor cellsregulatory lymphocytes