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Immunol."],"abstract":"<jats:p>Previous studies have reported the involvement of \u03b3\u03b4 T cells in recurrent spontaneous abortion (RSA); however, both pathogenic and protective effects were suggested. To interrogate the role of \u03b3\u03b4 T cells in RSA, peripheral blood from RSA patients and healthy women with or without pregnancy were analyzed for \u03b3\u03b4 T cells by flow cytometry (<jats:italic>n<\/jats:italic>= 9\u201311 for each group). Moreover, the decidua from pregnant RSA patients and healthy controls (RSA-P and HC-P group, respectively) was simultaneously stained for \u03b3\u03b4 T cells by immunohistochemistry (IHC) and bulk sequenced for gene expression. Our results demonstrated that the frequencies of peripheral \u03b3\u03b4 T cells and their subpopulations in RSA patients were comparable to that in healthy subjects, but the PD1 expression on V\u03b42<jats:sup>+<\/jats:sup>cells was increased in pregnant patients. Furthermore, peripheral V\u03b42<jats:sup>+<\/jats:sup>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\u03b42<jats:sup>+<\/jats:sup>cells compared to the control groups. In decidua, an inflammatory microenvironment was also evident in RSA-P patients, in which<jats:italic>CCL8<\/jats:italic>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 \u03b3\u03b4 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 \u03b3\u03b4 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 \u03b3\u03b4 T cells might be responsible for the pathogenesis of RSA. These findings could provide a better understanding of the role of \u03b3\u03b4 T cells in RSA and shed light on novel treatment strategies by targeting \u03b3\u03b4 T cells for RSA patients.<\/jats:p>","DOI":"10.3389\/fimmu.2021.724662","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T10:38:23Z","timestamp":1629196703000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Activated \u03b3\u03b4 T Cells With Higher CD107a Expression and Inflammatory Potential During Early Pregnancy in Patients With Recurrent Spontaneous Abortion"],"prefix":"10.3389","volume":"12","author":[{"given":"Long","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Zhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanjiang","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2004.12.018","article-title":"Evidence-Based 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