Fetal T cell activation in the amniotic cavity during preterm labor: a potential mechanism for a subset of idiopathic preterm birth

N Gomez-Lopez, R Romero, Y Xu, D Miller… - The Journal of …, 2019 - journals.aai.org
The Journal of Immunology, 2019journals.aai.org
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 …
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.
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