IFN- decreases PD-1 in T lymphocytes from convalescent COVID-19 patients via the AKT/GSK3 signaling pathway

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(+) T cells from recovered COVID-19 patients was significantly lower. IFN-gamma in the plasma of COVID-19 convalescent patients was increased, which inhibited PD-1 expression in CD8(+) T cells from COVID-19 convalescent patients. scRNA-seq bioinformatics analysis revealed that AKT/GSK3 beta may regulate the INF-gamma/PD-1 axis in CD8(+) T cells from COVID-19 convalescent patients. In parallel, an IFN-gamma neutralizing antibody reduced AKT and increased GSK3 beta in PBMCs. An AKT agonist (SC79) significantly decreased p-GSK3 beta. Moreover, AKT decreased PD-1 on CD8(+) T cells, and GSK3 beta increased PD-1 on CD8(+) T cells according to flow cytometry analysis. Collectively, we demonstrated that recovered COVID-19 patients may develop long COVID. Increased IFN-gamma in the plasma of recovered Wuhan COVID-19 patients contributed to PD-1 downregulation on CD8(+) T cells by regulating the AKT/GSK3 beta signaling pathway.