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

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

Author information

1
Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Detroit, MI 48201.
2
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201.
3
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, Mexico.
4
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109.
5
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI 48824.
6
Center for Molecular Obstetrics and Genetics, Wayne State University, Detroit, MI 48201.
7
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201.
8
Department of Computer Science, Wayne State University College of Engineering, Detroit, MI 48202; and.
9
Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Detroit, MI 48201; nardhy.gomez-lopez@wayne.edu.
10
Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI 48201.

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.

PMID:
30918041
PMCID:
PMC6570421
[Available on 2020-05-01]
DOI:
10.4049/jimmunol.1801350

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