Distinct Transcriptional and Alternative Splicing Signatures of Decidual CD4+ T Cells in Early Human Pregnancy

Abstract

Decidual CD4+ T (dCD4 T) cells are crucial for the maternal-fetal immune tolerance required for a healthy pregnancy outcome. However, their molecular and functional characteristics are not well elucidated. In this study, we performed the first analysis of transcriptional and alternative splicing (AS) landscapes for paired decidual and peripheral blood CD4+ T (pCD4 T) cells in human early pregnancy using high throughput mRNA sequencing. Our data showed that dCD4 T cells are endowed with a unique transcriptional signature when compared to pCD4 T cells: dCD4 T cells upregulate 1,695 genes enriched in immune system process whereas downregulate 1,011 genes mainly related to mRNA catabolic process and the ribosome. Moreover, dCD4 T cells were observed to be at M phase, and show increased activation, proliferation, and cytokine production, as well as display an effector-memory phenotype and a heterogenous nature containing Th1, Th17, and Treg cell subsets. However, dCD4 T cells undergo a comparable number of upregulated and downregulated AS events, both of which are enriched in the genes related to cellular metabolic process. And the changes at the AS event level do not reflect measurable differences at the gene expression level in dCD4 T cells. Collectively, our findings provide a comprehensive portrait of the unique transcriptional signature and AS profile of CD4+ T cells in human decidua and help us gain more understanding of the functional characteristic of these cells during early pregnancy.

PDL1 blockage increases fetal resorption and Tfr cells but does not affect Tfh/Tfr ratio and B-cell maturation during allogeneic pregnancy

“…Surface and intranuclear stainings were carried out by multicolor flow cytometry (FCM) as we and others described previously [34][35][36][37] . For cell surface staining, freshly isolated mononuclear cells were resuspended in 100 μL PBS containing 3% (v/v) fetal bovine serum (FBS) with different fluorescein-conjugated mAbs.…”

Biologic mechanisms and clinical consequences of pregnancy alloimmunization

“…Whether priming of the adaptive immune system occurs locally at the fetomaternal interface (in either the uterus or the placenta) remains unclear. Although maternal T and B cells populate both the uterine decidua 29,30 and the placenta (Lewis E, Sierra L-J, et al, in revision), studies of the uterine decidua during mouse pregnancy reveal that T cell trafficking into the decidua is limited. 31 Moreover, antigen presentation at the fetomaternal interface is quite altered compared to the secondary lymphoid organs, 32 and the human placental syncytiotrophoblast does not express classical HLA molecules that would promote T cell priming and differentiation.…”

Three macrophage subsets are identified in the uterus during early human pregnancy

“…Decidual T cells mainly include CD4+ helper T (Th) cells and CD8+ cytotoxic T cells. 1,22 Th1 and Th2 CD4 + T cells are found at the human maternal-fetal interface, and recurrent spontaneous abortion often correlates with an increased Th1/Th2 ratio. 1,23 However, few studies have clearly identified decidual macrophage subsets.…”