{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:02:50Z","timestamp":1792526570008,"version":"4.5.0"},"reference-count":55,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"810","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,8,6]]},"abstract":"<jats:p>\n            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\n            <jats:sup>+<\/jats:sup>\n            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\n            <jats:sup>+<\/jats:sup>\n            CD8\n            <jats:sup>+<\/jats:sup>\n            T cells in the peripheral blood of pregnant people in the second trimester, especially in those carrying a male fetus. In vitro, KIR\n            <jats:sup>+<\/jats:sup>\n            CD8\n            <jats:sup>+<\/jats:sup>\n            T cells inhibited the alloreactive responses of maternal T cells against irradiated cord blood cells and selectively suppressed CD8\n            <jats:sup>+<\/jats:sup>\n            T cells targeting male-specific proteins in mothers with male pregnancies. Therefore, the higher induction of KIR\n            <jats:sup>+<\/jats:sup>\n            CD8\n            <jats:sup>+<\/jats:sup>\n            T cells in mothers carrying a male fetus may help suppress additional allogeneic responses triggered by male-specific alloantigens. Longitudinal analysis showed that KIR\n            <jats:sup>+<\/jats:sup>\n            CD8\n            <jats:sup>+<\/jats:sup>\n            T cells undergo expansion and differentiate into functional cytotoxic cells during pregnancy. Single-cell RNA sequencing of decidual CD8\n            <jats:sup>+<\/jats:sup>\n            T cells from early pregnancy revealed elevated numbers and increased expression of activation markers in KIR\n            <jats:sup>+<\/jats:sup>\n            CD8\n            <jats:sup>+<\/jats:sup>\n            T cells at the maternal-fetal interface. In addition, a higher frequency of KIR\n            <jats:sup>+<\/jats:sup>\n            CD8\n            <jats:sup>+<\/jats:sup>\n            T cells was associated with spontaneous abortion and preeclampsia. Together, our findings suggest that KIR\n            <jats:sup>+<\/jats:sup>\n            CD8\n            <jats:sup>+<\/jats:sup>\n            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.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adm7697","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T17:59:19Z","timestamp":1754503159000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":15,"title":["Regulatory KIR\n            <sup>+<\/sup>\n            CD8\n            <sup>+<\/sup>\n            T cells are elevated during human pregnancy"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-9423","authenticated-orcid":true,"given":"Jing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA."},{"name":"University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA 15232, USA."},{"name":"Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6448-2676","authenticated-orcid":true,"given":"Xuerui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA."},{"name":"University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA 15232, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8034-0181","authenticated-orcid":true,"given":"Andreas I.","family":"Lackner","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purnima","family":"Narasimhan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8974-4636","authenticated-orcid":true,"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94158, USA."},{"name":"Center for Reproductive Sciences, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0658-3652","authenticated-orcid":true,"given":"Vamsee","family":"Mallajosyula","sequence":"additional","affiliation":[{"name":"Institute of Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5529-9378","authenticated-orcid":true,"given":"Anna-Lena","family":"H\u00f6bler","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Reproductive Biology Unit, Maternal-Fetal Immunology Group, Medical University of Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0500-9269","authenticated-orcid":true,"given":"Adam S.","family":"Kirosingh","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E.","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6011-9801","authenticated-orcid":true,"given":"Felistas","family":"Nankya","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Musinguzi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-1309","authenticated-orcid":true,"given":"Abel","family":"Kakuru","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9106-4234","authenticated-orcid":true,"given":"Moses","family":"Kamya","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Collaboration, Kampala, Uganda."},{"name":"Department of Medicine, Makerere University, Kampala, Uganda."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7953-7622","authenticated-orcid":true,"given":"Philip J.","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0740-0317","authenticated-orcid":true,"given":"Grant","family":"Dorsey","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Francisco, San Francisco, CA 94158, 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Vienna, 1090 Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0891-6964","authenticated-orcid":true,"given":"Stephanie L.","family":"Gaw","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94158, USA."},{"name":"Center for Reproductive Sciences, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1136-2907","authenticated-orcid":true,"given":"Virginia D.","family":"Winn","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA 94305, 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Chan School of Public Health, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6868-657X","authenticated-orcid":true,"given":"Mark M.","family":"Davis","sequence":"additional","affiliation":[{"name":"Institute of Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA."},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, 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Wang J. Li Elevation of KIR+CD8+ T cells during human pregnancy Zenodo [Dataset] (2025); https:\/\/zenodo.org\/records\/15345406."}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adm7697","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T17:59:20Z","timestamp":1754503160000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adm7697"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,6]]},"references-count":55,"journal-issue":{"issue":"810","published-print":{"date-parts":[[2025,8,6]]}},"alternative-id":["10.1126\/scitranslmed.adm7697"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adm7697","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,6]]},"assertion":[{"value":"2023-11-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-14","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadm7697"}}