TY - JOUR
T1 - Fetal T cell activation in the amniotic cavity during preterm labor
T2 - A potential mechanism for a subset of idiopathic preterm birth
AU - Gomez-Lopez, Nardhy
AU - Romero, Roberto
AU - Xu, Yi
AU - Miller, Derek
AU - Arenas-Hernandez, Marcia
AU - Garcia-Flores, Valeria
AU - Panaitescu, Bogdan
AU - Galaz, Jose
AU - Hsu, Chaur Dong
AU - Para, Robert
AU - Berry, Stanley M.
N1 - Funding Information:
Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/ NIH/DHHS) and in part with federal funds from NICHD/NIH/DHHS under Contract HHSN275201300006C. This research was also supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health.
Funding Information:
This work was supported in part by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/ NIH/DHHS) and in part with federal funds from NICHD/NIH/DHHS under Contract HHSN275201300006C. This research was also supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health. We thank the physicians, nurses, and research assistants from the Center for Advanced Obstetrical Care and Research, Intrapartum Unit, Perinatology Research Branch (PRB) Clinical Laboratory, and PRB Perinatal Translational Science Laboratory for help with collecting and processing samples. We would especially like to thank George Schwenkel for assistance with the animal experiments. We are grateful to Dr. Tippi C. MacKenzie for helpful discussions of the findings.
Funding Information:
This work was supported in part by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice
Publisher Copyright:
Copyright Ó 2019 by The American Association of Immunologists,
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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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U2 - 10.4049/jimmunol.1900621
DO - 10.4049/jimmunol.1900621
M3 - Article
C2 - 31492740
AN - SCOPUS:85072627598
VL - 203
SP - 1793
EP - 1807
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 7
ER -