人类妊娠期间调节性KIR + CD8 + T细胞升高

IF 14.6 1区 医学 Q1 CELL BIOLOGY
Jing Li, Xuerui Wang, Andreas I. Lackner, Purnima Narasimhan, Lin Li, Vamsee Mallajosyula, Mary M. Johnson, Anna-Lena Höbler, Adam S. Kirosingh, Amy E. Braun, Felistas Nankya, Kenneth Musinguzi, Abel Kakuru, Moses Kamya, Philip J. Rosenthal, Grant Dorsey, Prasanna Jagannathan, Michael Angelo, Jürgen Pollheimer, Stephanie L. Gaw, Virginia D. Winn, Kari C. Nadeau, Mark M. Davis
{"title":"人类妊娠期间调节性KIR + CD8 + T细胞升高","authors":"Jing Li, Xuerui Wang, Andreas I. Lackner, Purnima Narasimhan, Lin Li, Vamsee Mallajosyula, Mary M. Johnson, Anna-Lena Höbler, Adam S. Kirosingh, Amy E. Braun, Felistas Nankya, Kenneth Musinguzi, Abel Kakuru, Moses Kamya, Philip J. Rosenthal, Grant Dorsey, Prasanna Jagannathan, Michael Angelo, Jürgen Pollheimer, Stephanie L. Gaw, Virginia D. Winn, Kari C. Nadeau, Mark M. Davis","doi":"10.1126/scitranslmed.adm7697","DOIUrl":null,"url":null,"abstract":"During pregnancy, immune responses must balance protection from infections with tolerance of the semiallogeneic fetus. However, the mechanisms regulating maternal-fetal tolerance remain poorly understood. Recently, we identified CD8 <jats:sup>+</jats:sup> T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) as a regulatory subset important for suppressing self-reactivity in human autoimmune and infectious diseases. To better understand what other roles these cells might play, we asked whether they are active during pregnancy. We first observed an increased frequency of KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells in the peripheral blood of pregnant people in the second trimester, especially in those carrying a male fetus. In vitro, KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells inhibited the alloreactive responses of maternal T cells against irradiated cord blood cells and selectively suppressed CD8 <jats:sup>+</jats:sup> T cells targeting male-specific proteins in mothers with male pregnancies. Therefore, the higher induction of KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells in mothers carrying a male fetus may help suppress additional allogeneic responses triggered by male-specific alloantigens. Longitudinal analysis showed that KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells undergo expansion and differentiate into functional cytotoxic cells during pregnancy. Single-cell RNA sequencing of decidual CD8 <jats:sup>+</jats:sup> T cells from early pregnancy revealed elevated numbers and increased expression of activation markers in KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells at the maternal-fetal interface. In addition, a higher frequency of KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells was associated with spontaneous abortion and preeclampsia. Together, our findings suggest that KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells may contribute to maternal tolerance by modulating fetal-specific alloreactive T cell responses. They may also be useful as candidate biomarkers or therapeutic targets for human pregnancy disorders.","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"27 1","pages":""},"PeriodicalIF":14.6000,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Regulatory KIR + CD8 + T cells are elevated during human pregnancy\",\"authors\":\"Jing Li, Xuerui Wang, Andreas I. Lackner, Purnima Narasimhan, Lin Li, Vamsee Mallajosyula, Mary M. Johnson, Anna-Lena Höbler, Adam S. Kirosingh, Amy E. Braun, Felistas Nankya, Kenneth Musinguzi, Abel Kakuru, Moses Kamya, Philip J. Rosenthal, Grant Dorsey, Prasanna Jagannathan, Michael Angelo, Jürgen Pollheimer, Stephanie L. Gaw, Virginia D. Winn, Kari C. Nadeau, Mark M. Davis\",\"doi\":\"10.1126/scitranslmed.adm7697\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"During pregnancy, immune responses must balance protection from infections with tolerance of the semiallogeneic fetus. However, the mechanisms regulating maternal-fetal tolerance remain poorly understood. Recently, we identified CD8 <jats:sup>+</jats:sup> T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) as a regulatory subset important for suppressing self-reactivity in human autoimmune and infectious diseases. To better understand what other roles these cells might play, we asked whether they are active during pregnancy. We first observed an increased frequency of KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells in the peripheral blood of pregnant people in the second trimester, especially in those carrying a male fetus. In vitro, KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells inhibited the alloreactive responses of maternal T cells against irradiated cord blood cells and selectively suppressed CD8 <jats:sup>+</jats:sup> T cells targeting male-specific proteins in mothers with male pregnancies. Therefore, the higher induction of KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells in mothers carrying a male fetus may help suppress additional allogeneic responses triggered by male-specific alloantigens. Longitudinal analysis showed that KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells undergo expansion and differentiate into functional cytotoxic cells during pregnancy. Single-cell RNA sequencing of decidual CD8 <jats:sup>+</jats:sup> T cells from early pregnancy revealed elevated numbers and increased expression of activation markers in KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells at the maternal-fetal interface. In addition, a higher frequency of KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells was associated with spontaneous abortion and preeclampsia. Together, our findings suggest that KIR <jats:sup>+</jats:sup> CD8 <jats:sup>+</jats:sup> T cells may contribute to maternal tolerance by modulating fetal-specific alloreactive T cell responses. They may also be useful as candidate biomarkers or therapeutic targets for human pregnancy disorders.\",\"PeriodicalId\":21580,\"journal\":{\"name\":\"Science Translational Medicine\",\"volume\":\"27 1\",\"pages\":\"\"},\"PeriodicalIF\":14.6000,\"publicationDate\":\"2025-08-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Science Translational Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1126/scitranslmed.adm7697\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1126/scitranslmed.adm7697","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

在怀孕期间,免疫反应必须平衡对感染的保护和对半异体胎儿的耐受。然而,调节母胎耐受性的机制仍然知之甚少。最近,我们发现表达抑制性杀伤细胞免疫球蛋白样受体(KIRs)的CD8 + T细胞是抑制人类自身免疫性和感染性疾病的自我反应性的重要调控亚群。为了更好地了解这些细胞可能发挥的其他作用,我们询问它们在怀孕期间是否活跃。我们首先观察到妊娠中期孕妇外周血中KIR + CD8 + T细胞的频率增加,尤其是那些怀男性胎儿的孕妇。在体外实验中,KIR + CD8 + T细胞抑制了母体T细胞对辐照脐带血细胞的同种异体反应,并选择性地抑制了男性妊娠母亲的靶向男性特异性蛋白的CD8 + T细胞。因此,在携带男性胎儿的母亲中,KIR + CD8 + T细胞的高诱导可能有助于抑制男性特异性同种异体抗原引发的额外异体反应。纵向分析表明,KIR + CD8 + T细胞在妊娠期间扩增并分化为功能性细胞毒细胞。妊娠早期个体CD8 + T细胞的单细胞RNA测序显示,母胎界面KIR + CD8 + T细胞中激活标记物的数量和表达增加。此外,KIR + CD8 + T细胞频率较高与自然流产和先兆子痫有关。总之,我们的研究结果表明,KIR + CD8 + T细胞可能通过调节胎儿特异性同种异体反应性T细胞反应来促进母体耐受。它们也可能是人类妊娠障碍的候选生物标志物或治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Regulatory KIR + CD8 + T cells are elevated during human pregnancy
During pregnancy, immune responses must balance protection from infections with tolerance of the semiallogeneic fetus. However, the mechanisms regulating maternal-fetal tolerance remain poorly understood. Recently, we identified CD8 + T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) as a regulatory subset important for suppressing self-reactivity in human autoimmune and infectious diseases. To better understand what other roles these cells might play, we asked whether they are active during pregnancy. We first observed an increased frequency of KIR + CD8 + T cells in the peripheral blood of pregnant people in the second trimester, especially in those carrying a male fetus. In vitro, KIR + CD8 + T cells inhibited the alloreactive responses of maternal T cells against irradiated cord blood cells and selectively suppressed CD8 + T cells targeting male-specific proteins in mothers with male pregnancies. Therefore, the higher induction of KIR + CD8 + T cells in mothers carrying a male fetus may help suppress additional allogeneic responses triggered by male-specific alloantigens. Longitudinal analysis showed that KIR + CD8 + T cells undergo expansion and differentiate into functional cytotoxic cells during pregnancy. Single-cell RNA sequencing of decidual CD8 + T cells from early pregnancy revealed elevated numbers and increased expression of activation markers in KIR + CD8 + T cells at the maternal-fetal interface. In addition, a higher frequency of KIR + CD8 + T cells was associated with spontaneous abortion and preeclampsia. Together, our findings suggest that KIR + CD8 + T cells may contribute to maternal tolerance by modulating fetal-specific alloreactive T cell responses. They may also be useful as candidate biomarkers or therapeutic targets for human pregnancy disorders.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Science Translational Medicine
Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
26.70
自引率
1.20%
发文量
309
审稿时长
1.7 months
期刊介绍: Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信