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

Sci Rep. 2024 Feb 29;14(1):5038. doi: 10.1038/s41598-024-55191-6.

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+ 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+ 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+ 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+ T cells, and GSK3β 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-γ in the plasma of recovered Wuhan COVID-19 patients contributed to PD-1 downregulation on CD8+ T cells by regulating the AKT/GSK3β signaling pathway.

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

MeSH terms

  • Aged
  • CD8-Positive T-Lymphocytes*
  • COVID-19* / metabolism
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Post-Acute COVID-19 Syndrome
  • Programmed Cell Death 1 Receptor / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction

Substances

  • Glycogen Synthase Kinase 3 beta
  • Interferon-gamma
  • Programmed Cell Death 1 Receptor
  • Proto-Oncogene Proteins c-akt
  • PDCD1 protein, human
  • IFNG protein, human