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Fetal T Cell Activation in the Amniotic Cavity during Preterm Labor: A Potential Mechanism for a Subset of Idiopathic Preterm Birth.


ABSTRACT: Prematurity is the leading cause of perinatal morbidity and mortality worldwide. In most cases, preterm birth is preceded by spontaneous preterm labor, a syndrome that is associated with intra-amniotic inflammation, the most studied etiology. However, the remaining etiologies of preterm labor are poorly understood; therefore, most preterm births are categorized as idiopathic. In this study, we provide evidence showing that the fetal immune system undergoes premature activation in women with preterm labor without intra-amniotic inflammation, providing a potential new mechanism of disease for some cases of idiopathic preterm birth. First, we showed that fetal T cells are a predominant leukocyte population in amniotic fluid during preterm gestations. Interestingly, only fetal CD4+ T cells were increased in amniotic fluid of women who underwent idiopathic preterm labor and birth. This increase in fetal CD4+ T cells was accompanied by elevated amniotic fluid concentrations of T cell cytokines such as IL-2, IL-4, and IL-13, which are produced by these cells upon in vitro stimulation, but was not associated with the prototypical cytokine profile observed in women with intra-amniotic inflammation. Also, we found that cord blood T cells, mainly CD4+ T cells, obtained from women with idiopathic preterm labor and birth displayed enhanced ex vivo activation, which is similar to that observed in women with intra-amniotic inflammation. Finally, we showed that the intra-amniotic administration of activated neonatal CD4+ T cells induces preterm birth in mice. Collectively, these findings provide evidence suggesting that fetal T cell activation is implicated in the pathogenesis of idiopathic preterm labor and birth.

SUBMITTER: Gomez-Lopez N 

PROVIDER: S-EPMC6799993 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Fetal T Cell Activation in the Amniotic Cavity during Preterm Labor: A Potential Mechanism for a Subset of Idiopathic Preterm Birth.

Gomez-Lopez Nardhy N   Romero Roberto R   Xu Yi Y   Miller Derek D   Arenas-Hernandez Marcia M   Garcia-Flores Valeria V   Panaitescu Bogdan B   Galaz Jose J   Galaz Jose J   Hsu Chaur-Dong CD   Para Robert R   Berry Stanley M SM  

Journal of immunology (Baltimore, Md. : 1950) 20190906 7


Prematurity is the leading cause of perinatal morbidity and mortality worldwide. In most cases, preterm birth is preceded by spontaneous preterm labor, a syndrome that is associated with intra-amniotic inflammation, the most studied etiology. However, the remaining etiologies of preterm labor are poorly understood; therefore, most preterm births are categorized as idiopathic. In this study, we provide evidence showing that the fetal immune system undergoes premature activation in women with pret  ...[more]

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