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Here, we define a population of TCR\u03b2\n                    <jats:sup>+<\/jats:sup>\n                    NK1.1\n                    <jats:sup>\u2212<\/jats:sup>\n                    DNTs enriched in the mouse ovary and uterus and profiled its phenotype, tissue behavior, and function in inflammatory models associated with impaired fertility. In parallel, we performed RNA-seq on spleen- and thymus-derived NK1.1\n                    <jats:sup>\u2212<\/jats:sup>\n                    DNT and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell enriched population. Relative to CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, peripheral NK1.1\n                    <jats:sup>\u2212<\/jats:sup>\n                    DN T-cell-enriched populations displayed an activated, regulatory-like transcriptional profile with reduced\n                    <jats:italic>Cd8a<\/jats:italic>\n                    \/\n                    <jats:italic>Cd8b1<\/jats:italic>\n                    ,\n                    <jats:italic>Il7r<\/jats:italic>\n                    , and cytotoxic effector markers, alongside increased expression of\n                    <jats:italic>Pdcd1<\/jats:italic>\n                    ,\n                    <jats:italic>Lag3<\/jats:italic>\n                    ,\n                    <jats:italic>Tox<\/jats:italic>\n                    , and\n                    <jats:italic>Il10<\/jats:italic>\n                    . Ex vivo, FACS-sorted splenic DNTs produced low inflammatory cytokine output after CD3\/CD28 stimulation and suppressed CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell proliferation primarily through contact-dependent mechanisms. In vivo, ovarian DNTs decreased following CD8-targeting depletion, and ovarian and uterine DNTs showed limited exchange in parabiosis. In chronic interferon-\u03b3-driven inflammation (ARE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) and zona pellucida 3-induced ovarian inflammation, reproductive tissues exhibited reduced DNT frequencies, a shift in the DNT: CD8\n                    <jats:sup>+<\/jats:sup>\n                    T ratio favoring CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and increased activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    phenotypes. Finally, adoptive transfer of ex vivo FACS-sorted wild-type DNTs into ARE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    females increased pregnancy frequency, supporting DNT-associated immunoregulation as a feature of inflammation-associated infertility.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-57959-4","type":"journal-article","created":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T10:35:34Z","timestamp":1782038134000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Double negative T cells decline in inflammatory reproductive dysfunction"],"prefix":"10.1038","volume":"16","author":[{"given":"Enitome E.","family":"Bafor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna Karoline","family":"Tatematsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian A.","family":"Bettencourt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne E.","family":"Kimmel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy K.","family":"Sojka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard A.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,21]]},"reference":[{"key":"57959_CR1","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.3201\/eid1011.040367","volume":"10","author":"D Fairweather","year":"2004","unstructured":"Fairweather, D. & Rose, N. 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