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Sci Rep . IFN-γ decreases PD-1 in T lymphocytes from convalescent COVID-19 patients via the AKT/GSK3β signaling pathway

tetano

Editor, Senior Moderator
Sci Rep


. 2024 Feb 29;14(1):5038.
doi: 10.1038/s41598-024-55191-6. IFN-γ decreases PD-1 in T lymphocytes from convalescent COVID-19 patients via the AKT/GSK3β signaling pathway

Meijuan Song[SUP] #[/SUP][SUP] 1 [/SUP], Xiangqun Liu[SUP] #[/SUP][SUP] 2 [/SUP], Weiyu Shen[SUP] #[/SUP][SUP] 3 [/SUP], Zhengxia Wang[SUP] 1 [/SUP], Jingjing Wu[SUP] 1 [/SUP], Jingxian Jiang[SUP] 1 [/SUP], Yanan Liu[SUP] 1 [/SUP], Tingting Xu[SUP] 1 [/SUP], Tao Bian[SUP] 3 [/SUP], Mingshun Zhang[SUP] 4 [/SUP], Wei Sun[SUP] 5 [/SUP], Mao Huang[SUP] 6 [/SUP], Ningfei Ji[SUP] 7 [/SUP]



Affiliations
Abstract

Post-COVID-19 syndrome may be associated with the abnormal immune status. Compared with the unexposed age-matched elder group, PD-1 in the CD8[SUP]+[/SUP] T cells from recovered COVID-19 patients was significantly lower. IFN-γ in the plasma of COVID-19 convalescent patients was increased, which inhibited PD-1 expression in CD8[SUP]+[/SUP] T cells from COVID-19 convalescent patients. scRNA-seq bioinformatics analysis revealed that AKT/GSK3β may regulate the INF-γ/PD-1 axis in CD8[SUP]+[/SUP] T cells from COVID-19 convalescent patients. In parallel, an IFN-γ neutralizing antibody reduced AKT and increased GSK3β in PBMCs. An AKT agonist (SC79) significantly decreased p-GSK3β. Moreover, AKT decreased PD-1 on CD8[SUP]+[/SUP] T cells, and GSK3β increased PD-1 on CD8[SUP]+[/SUP] T cells according to flow cytometry analysis. Collectively, we demonstrated that recovered COVID-19 patients may develop long COVID. Increased IFN-γ in the plasma of recovered Wuhan COVID-19 patients contributed to PD-1 downregulation on CD8[SUP]+[/SUP] T cells by regulating the AKT/GSK3β signaling pathway.

Keywords: CD8+ T cells; Convalescent patients; Coronavirus disease 2019; IFN-γ; PD-1.

 
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