ICOS-ICOSL pathway enhances NKT-like cell antiviral function in pregnant women with COVID-19

Int J Med Sci. 2024 Jul 16;21(10):1890-1902. doi: 10.7150/ijms.95952. eCollection 2024.

Abstract

Objective: The immune response initiated by SARS-CoV-2 infection in pregnancy is poorly elucidated. We aimed to access and compare the antiviral cellular responses and lymphocytes activation between healthy pregnancies and pregnant women infected with SARS-CoV-2. Methods: We detected the immunological changes of lymphocytes in peripheral blood of healthy non-pregnant women, non-pregnant women with COVID-19, healthy pregnant women, pregnant women with COVID-19 and convalescent group by flow cytometry. In vitro blockade was used to identify NKT-like cell activation through ICOS-ICOSL pathway. Results: We found that CD3+CD56+ NKT-like cells decreased significantly in COVID-19 positive pregnant women compared to healthy pregnant women. NKT-like cells of pregnant women expressed higher level of activating receptors CD69 and NKp46 after SARS-CoV-2 infection. Particularly, they also increased the expression of the co-stimulatory molecule ICOS. NKT-like cells of pregnant women with COVID-19 up-regulated the expression of IFN-γ, CD107a and Ki67. Meanwhile, we found that ICOSL expression was significantly increased on pDCs in pregnant women with COVID-19. Blocking ICOS in vitro significantly decreased the antiviral activity of NKT-like cells in COVID-19 positive pregnant women, suggesting that ICOS-ICOSL may play an important role in the virus clearance by NKT-like cells. Conclusions: During SARS-CoV-2 infection, NKT-like cells of pregnant women activated through ICOS-ICOSL pathway and played an important role in the antiviral response.

Keywords: CD3+CD56+ NKT-like cells; COVID-19; ICOS; Pregnancy.

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • COVID-19* / immunology
  • COVID-19* / virology
  • Female
  • Humans
  • Inducible T-Cell Co-Stimulator Ligand* / metabolism
  • Inducible T-Cell Co-Stimulator Protein* / metabolism
  • Interferon-gamma / metabolism
  • Lectins, C-Type / metabolism
  • Lymphocyte Activation / immunology
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism
  • Natural Killer T-Cells* / immunology
  • Natural Killer T-Cells* / metabolism
  • Pregnancy
  • Pregnancy Complications, Infectious* / immunology
  • Pregnancy Complications, Infectious* / virology
  • SARS-CoV-2* / immunology
  • Signal Transduction / immunology

Substances

  • Inducible T-Cell Co-Stimulator Protein
  • ICOS protein, human
  • Inducible T-Cell Co-Stimulator Ligand
  • ICOSLG protein, human
  • Antigens, CD
  • CD69 antigen
  • Antigens, Differentiation, T-Lymphocyte
  • Interferon-gamma
  • Natural Cytotoxicity Triggering Receptor 1
  • NCR1 protein, human
  • Lectins, C-Type