Abstract
Previous studies have reported the involvement of γδ T cells in recurrent spontaneous abortion (RSA); however, both pathogenic and protective effects were suggested. To interrogate the role of γδ T cells in RSA, peripheral blood from RSA patients and healthy women with or without pregnancy were analyzed for γδ 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 γδ T cells by immunohistochemistry (IHC) and bulk sequenced for gene expression. Our results demonstrated that the frequencies of peripheral γδ T cells and their subpopulations in RSA patients were comparable to that in healthy subjects, but the PD1 expression on Vδ2+ cells was increased in pregnant patients. Furthermore, peripheral Vδ2+ 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 Vδ2+ 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 γδ 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 γδ 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 γδ T cells might be responsible for the pathogenesis of RSA. These findings could provide a better understanding of the role of γδ T cells in RSA and shed light on novel treatment strategies by targeting γδ T cells for RSA patients.
Highlights
With an incidence of 1%–3% worldwide [1, 2], recurrent spontaneous abortion (RSA) was defined as two or more consecutive pregnancy losses prior to the 20th week of gestation
Our results indicated that the frequency of gd T cells was unchanged in RSA patients compared to healthy controls and was relatively stable during physiological and pathological pregnancy
Our result showed a higher expression of CD107a in RSA-P patients compared to HC-P controls (Figure 5B and Supplementary Figure S5C), and the co-localization of CD107a and gd T cells can be found in RSA-P patients but rarely in healthy controls
Summary
With an incidence of 1%–3% worldwide [1, 2], RSA was defined as two or more consecutive pregnancy losses prior to the 20th week of gestation. Increasing evidence has suggested that URSA likely results from local (i.e., maternal–fetal interface) or systemic immune disorder. Maternal immune system is better pro-inflammatory to allow the successful implantation and placentation, and it must be subsequently switched to be anti-inflammatory to support fetal growth during the second trimester. In the third trimester, a second inflammatory response is necessary for the initiation of parturition. In this scenario, multiple immune cells have to coordinate to create an optimal immune milieu both at the maternal–fetal interface and in periphery for the success of pregnancy. Changes of NK cells, macrophages, neutrophils, and ab T cells during heathy pregnancy and RSA have been extensively investigated [6]; the role of gd T cells remains less characterized
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