{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:27:23Z","timestamp":1781915243758,"version":"3.54.5"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,6,19]],"date-time":"2016-06-19T00:00:00Z","timestamp":1466294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI102838"],"award-info":[{"award-number":["AI102838"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI117739"],"award-info":[{"award-number":["AI117739"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec><jats:title>Problem<\/jats:title><jats:p>The programmed death 1 (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101)\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 pathway regulates peripheral tolerance, immune responses, and is up\u2010regulated in chronic viral infections, including <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> infection. However, expression of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 on immune cells from the human female reproductive tract (<jats:styled-content style=\"fixed-case\">FRT<\/jats:styled-content>) and possible regulation by menopause and sex hormones are poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 expression was analyzed on <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>163<jats:sup>+<\/jats:sup> macrophages, and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>11c<jats:sup>+<\/jats:sup> dendritic cells (<jats:styled-content style=\"fixed-case\">DC<\/jats:styled-content>) from endometrium (<jats:styled-content style=\"fixed-case\">EM<\/jats:styled-content>), endocervix (<jats:styled-content style=\"fixed-case\">CX<\/jats:styled-content>) and ectocervix (<jats:styled-content style=\"fixed-case\">ECX<\/jats:styled-content>). Expression after hormone treatment in culture was also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 and <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 were constitutively expressed on <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells from the <jats:styled-content style=\"fixed-case\">FRT<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1<jats:sup>+<\/jats:sup><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> T cells were increased in <jats:styled-content style=\"fixed-case\">CX<\/jats:styled-content> compared to <jats:styled-content style=\"fixed-case\">EM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ECX<\/jats:styled-content>, while no differences were found for <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 or between <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells from different sites. Macrophages and <jats:styled-content style=\"fixed-case\">DC<\/jats:styled-content>s constitutively expressed <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1, but not <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101, with no differences observed between <jats:styled-content style=\"fixed-case\">FRT<\/jats:styled-content> sites. Pre\u2010menopausal <jats:styled-content style=\"fixed-case\">FRT<\/jats:styled-content> tissues showed increased <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 expression on <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells, but decreased expression on <jats:styled-content style=\"fixed-case\">DC<\/jats:styled-content>s when compared to post\u2010menopausal women. In vitro estradiol treatment up\u2010regulated <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 expression specifically on <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup>T cells from <jats:styled-content style=\"fixed-case\">CX<\/jats:styled-content>, but had no effect on <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 expression on the other cell types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 may be involved in the differential regulation of <jats:styled-content style=\"fixed-case\">FRT<\/jats:styled-content> immune responses between pre\u2010menopausal and post\u2010menopausal 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