Exhausted and Senescent T Cells at the Maternal-Fetal Interface in Preterm and Term Labor

J Immunol Res. 2019 May 23:2019:3128010. doi: 10.1155/2019/3128010. eCollection 2019.

Abstract

Successful pregnancy requires a tightly-regulated equilibrium of immune cell interactions at the maternal-fetal interface (i.e., the decidual tissues), which plays a central role in the inflammatory process of labor. Most of the innate immune cells in this compartment have been well characterized; however, adaptive immune cells are still under investigation. Herein, we performed immunophenotyping of the decidua basalis and decidua parietalis to determine whether exhausted and senescent T cells are present at the maternal-fetal interface and whether the presence of pathological (i.e., preterm) or physiological (i.e., term) labor and/or placental inflammation alter such adaptive immune cells. In addition, decidual exhausted T cells were sorted to test their functional status. We found that (1) exhausted and senescent T cells were present at the maternal-fetal interface and predominantly expressed an effector memory phenotype, (2) exhausted CD4+ T cells increased in the decidua parietalis as gestational age progressed, (3) exhausted CD4+ and CD8+ T cells decreased in the decidua basalis of women who underwent labor at term compared to those without labor, (4) exhausted CD4+ T cells declined with the presence of placental inflammation in the decidua basalis of women with preterm labor, (5) exhausted CD8+ T cells decreased with the presence of placental inflammation in the decidua basalis of women who underwent labor at term, (6) both senescent CD4+ and CD8+ T cells declined with the presence of placental inflammation in the decidua basalis of women who underwent preterm labor, and (7) decidual exhausted T cells produced IFNγ and TNFα upon in vitro stimulation. Collectively, these findings indicate that exhausted and senescent T cells are present at the human maternal-fetal interface and undergo alterations in a subset of women either with labor at term or preterm labor and placental inflammation. Importantly, decidual T cell function can be restored upon stimulation.

MeSH terms

  • Adult
  • Biomarkers
  • Cellular Senescence / immunology
  • Decidua / immunology
  • Decidua / metabolism
  • Female
  • Humans
  • Immunophenotyping
  • Labor, Obstetric / immunology*
  • Labor, Obstetric / metabolism
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Lymphocyte Count
  • Maternal-Fetal Exchange / immunology*
  • Obstetric Labor, Premature / immunology*
  • Obstetric Labor, Premature / metabolism
  • Placenta / immunology*
  • Placenta / metabolism
  • Pregnancy
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Young Adult

Substances

  • Biomarkers