Early pregnancy human decidua gamma/delta T cells exhibit tissue resident and specific functional characteristics

Abstract

A successful pregnancy is a complicated process that builds upon two aspects of the maternal immune system that need to be balanced. As one of the indispensable groups of immune cell at the maternal-fetal interface, the decidual gamma/delta (γδ) T cells have attracted research attention in normal pregnancy and miscarriage. However, the role of γδ T cells in fetal growth remains poorly understood. Here we found that the γδ T cell population resident in decidua during early pregnancy was enriched and secreted growth factors including growth differentiation factor 15 (GDF15) and bone morphogenetic protein 1 (BMP1). A diminution in such growth factors may impair fetal development and result in fetal growth restriction. We also observed that early decidual γδ T cells exhibited stronger cytokine-secretion characteristics, but that their cytotoxic actions against A549 cells were weaker, compared with γδ T cells in peripheral blood mononuclear cells (PBMCs). In addition, the functional abilities of early decidual γδ T cells in promoting trophoblast cell proliferation, migration, invasion, and tube formation were also significantly more robust than in γδ T cells of PBMCs. These findings highlight the importance of γδ T cells in fetal growth and maternal immunotolerance during pregnancy, and show that they differ from γδ T cells in PBMCs. We thus recommend additional investigation in this research area to further elucidate a role for γδ T cells in pregnancy.

Human chorionic gonadotrophin indirectly activates peripheral γδT cells to produce interleukin‐10 during early pregnancy

“…In addition, the hCG values of patients with miscarriage usually decrease, 40 and the comparisons between normal nonpregnant women, normal pregnant women, and miscarriage women (related hCG concentrations) are also worth studying in the future. We only proposed certain immune effective functions of peripheral γδT cells may be indirectly affected by hCG; however, it has been reported that γδT cells are capable of secreting growth factors in early pregnancy, such as growth differentiation factor 15 (GDF15) and bone morphogenetic protein 1 (BMP1) 24 . Whether hCG can affect more versatile functions of γδT cells is also worth investigating.…”

“…We only proposed certain immune effective functions of peripheral γδT cells may be indirectly affected by hCG; however, it has been reported that γδT cells are capable of secreting growth factors in early pregnancy, such as growth differentiation factor 15 (GDF15) and bone morphogenetic protein 1 (BMP1). 24 Whether hCG can affect more versatile functions of γδT cells is also worth investigating.…”

“…Flow cytometry data were acquired on a FACS Celesta flow cytometer (BD), and analyzed using FlowJo software V.10. For the use of monoclonal antibodies, we referred to our published study 24 and the details can be found in Supporting Information: Table 1 .…”

Double-edged sword: γδ T cells in mucosal homeostasis and disease

“…Decidual γδ T cells also produce growth factors such as IGFBP2, VEGFC, GDF15, and BMP1, and the expression levels of these growth factors are significantly decreased in patients with recurrent abortion. These growth factor-producing γδ T cells have been shown to promote the migration, invasion, and proliferation of trophoblasts 61 .…”