Effector and Activated T Cells Induce Preterm Labor and Birth That Is Prevented by Treatment with Progesterone

J Immunol. 2019 May 1;202(9):2585-2608. doi: 10.4049/jimmunol.1801350. Epub 2019 Mar 27.

Abstract

Preterm labor commonly precedes preterm birth, the leading cause of perinatal morbidity and mortality worldwide. Most research has focused on establishing a causal link between innate immune activation and pathological inflammation leading to preterm labor and birth. However, the role of maternal effector/activated T cells in the pathogenesis of preterm labor/birth is poorly understood. In this study, we first demonstrated that effector memory and activated maternal T cells expressing granzyme B and perforin are enriched at the maternal-fetal interface (decidua) of women with spontaneous preterm labor. Next, using a murine model, we reported that prior to inducing preterm birth, in vivo T cell activation caused maternal hypothermia, bradycardia, systemic inflammation, cervical dilation, intra-amniotic inflammation, and fetal growth restriction, all of which are clinical signs associated with preterm labor. In vivo T cell activation also induced B cell cytokine responses, a proinflammatory macrophage polarization, and other inflammatory responses at the maternal-fetal interface and myometrium in the absence of an increased influx of neutrophils. Finally, we showed that treatment with progesterone can serve as a strategy to prevent preterm labor/birth and adverse neonatal outcomes by attenuating the proinflammatory responses at the maternal-fetal interface and cervix induced by T cell activation. Collectively, these findings provide mechanistic evidence showing that effector and activated T cells cause pathological inflammation at the maternal-fetal interface, in the mother, and in the fetus, inducing preterm labor and birth and adverse neonatal outcomes. Such adverse effects can be prevented by treatment with progesterone, a clinically approved strategy.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes* / immunology
  • B-Lymphocytes* / pathology
  • Female
  • Humans
  • Lymphocyte Activation / drug effects*
  • Placenta* / immunology
  • Placenta* / pathology
  • Pregnancy
  • Premature Birth* / immunology
  • Premature Birth* / pathology
  • Premature Birth* / prevention & control
  • Progesterone / administration & dosage*
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / pathology

Substances

  • Progesterone