Examination of the TIGIT-CD226-CD112-CD155 Immune Checkpoint Network during a Healthy Pregnancy

Int J Mol Sci. 2022 Sep 15;23(18):10776. doi: 10.3390/ijms231810776.


Background: The importance of immune checkpoint molecules is well known in tumor and transplantation immunology; however, much less information is available regarding human pregnancy. Despite the significant amount of information about the TIGIT and CD226 immune checkpoint receptors in immune therapies, very little research has been conducted to study the possible role of these surface molecules and their ligands (CD112 and CD155) during the three trimesters of pregnancy. Methods: From peripheral blood, immune cell subpopulations were studied, and the surface expression of immune checkpoint molecules was analyzed by flow cytometry. Soluble immune checkpoint molecule levels were measured by ELISA. Results: Notable changes were observed regarding the percentage of monocyte subpopulation and the expression of CD226 receptor by CD4+ T and NKT cells. Elevated granzyme B content by the intermediate and non-classical monocytes was assessed as pregnancy proceeded. Furthermore, we revealed an important relationship between the CD226 surface expression by NKT cells and the serum CD226 level in the third trimester of pregnancy. Conclusions: Our results confirm the importance of immune checkpoint molecules in immunoregulation during pregnancy. CD226 seems to be a significant regulator, especially in the case of CD4+ T and NKT cells, contributing to the maternal immune tolerance in the late phase of pregnancy.

Keywords: CD112; CD155; CD226; TIGIT; immune checkpoint; pregnancy.

MeSH terms

  • Antigens, Differentiation, T-Lymphocyte* / metabolism
  • Female
  • Granzymes
  • Humans
  • Immune Checkpoint Proteins
  • Natural Killer T-Cells* / metabolism
  • Pregnancy
  • Receptors, Immunologic / metabolism
  • Receptors, Virus / metabolism


  • Antigens, Differentiation, T-Lymphocyte
  • Immune Checkpoint Proteins
  • Receptors, Immunologic
  • Receptors, Virus
  • TIGIT protein, human
  • Granzymes

Grants and funding

This work was supported by the University of Pecs Medical School Research Grant (PTE-ÁOK KA 2021-20, KA 2021-38, KA 2019-48) and the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences to M. Meggyes.