Activated Gamma Delta T Cells With Higher Cd107a Expression And Inflammatory Potential During Early Pregnancy In Patients With Recurrent Spontaneous Abortion

Previous studies have reported the involvement of gamma delta T cells in recurrent spontaneous abortion (RSA); however, both pathogenic and protective effects were suggested. To interrogate the role of gamma delta T cells in RSA, peripheral blood from RSA patients and healthy women with or without pregnancy were analyzed for gamma delta T cells by flow cytometry (n = 9-11 for each group). Moreover, the decidua from pregnant RSA patients and healthy controls (RSA-P and HC-P group, respectively) was simultaneously stained for gamma delta T cells by immunohistochemistry (IHC) and bulk sequenced for gene expression. Our results demonstrated that the frequencies of peripheral gamma delta T cells and their subpopulations in RSA patients were comparable to that in healthy subjects, but the PD1 expression on V delta 2(+) cells was increased in pregnant patients. Furthermore, peripheral V delta 2(+) cells in RSA-P patients demonstrated significantly increased expression of CD107a, as compared to that in pregnant healthy controls. In addition, RSA-P patients had higher proportion of IL-17A-secreting but not IL-4-secreting V delta 2(+) cells compared to the control groups. In decidua, an inflammatory microenvironment was also evident in RSA-P patients, in which CCL8 expression and the infiltration of certain immune cells were higher than that in the HC-P group, as revealed by transcriptional analysis. Finally, although the presence of gamma delta T cells in decidua could be detected during pregnancy in both RSA patients and healthy subjects by multicolor IHC analysis, the expression of CD107a on gamma delta T cells was markedly higher in the RSA-P group. Collectively, our results indicated that the increased activation, cytotoxicity, and inflammatory potential of peripheral and/or local gamma delta T cells might be responsible for the pathogenesis of RSA. These findings could provide a better understanding of the role of gamma delta T cells in RSA and shed light on novel treatment strategies by targeting gamma delta T cells for RSA patients.