Activated γδ T Cells With Higher CD107a Expression and Inflammatory Potential During Early Pregnancy in Patients With Recurrent Spontaneous Abortion

• Published in: Frontiers in immunology Vol. 12; p. 724662
• Main Authors: Yu, Long, Zhang, Yang, Xiong, Jinfeng, Liu, Jianjun, Zha, Ying, Kang, Qi, Zhi, Pan, Wang, Qiang, Wang, Hui, Zeng, Wanjiang, Huang, Yafei
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 17.08.2021
• Subjects: Abortion, Habitual - blood; Abortion, Habitual - pathology; Adult; Case-Control Studies; CD107a; Decidua - metabolism; Decidua - pathology; Female; Flow Cytometry; Humans; IL-17A; Immunology; Interleukin-17 - blood; Lysosomal-Associated Membrane Protein 1 - blood; PD1; Pregnancy; Receptors, Antigen, T-Cell, gamma-delta; recurrent spontaneous abortion (RSA); T-Lymphocytes - metabolism; T-Lymphocytes - pathology; Young Adult; γδ T cells; γδ T cells; recurrent spontaneous abortion (RSA); CD107a; IL-17A; PD1
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.724662

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.