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 ( = 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 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.