{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T05:41:19Z","timestamp":1770097279841,"version":"3.49.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2004,7,1]],"date-time":"2004-07-01T00:00:00Z","timestamp":1088640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A model of neonatal autoimmune disease has been described recently in which an epitope-specific autoantibody to murine zona pellucida 3 induces severe ovarian disease in neonatal, but not adult, mice (neonatal AOD). The autoantibody forms immune complex with endogenous ovarian zona pellucida 3, and a pathogenic CD4+ T cell response is triggered. The basis for the predominant neonatal susceptibility has not been clarified. In this study innate immunity, including neonatal NK cells, in neonatal AOD was investigated. Neonatal spleen contained readily detectable NK1.1+TCRV\u03b2\u2212, but not NK1.1+TCRV\u03b2+, cells. Ab depletion of NK1.1+TCRV\u03b2\u2212 cells inhibited neonatal AOD development. Moreover, in adoptive transfer of neonatal AOD, recipient disease was ameliorated when either donor or recipient NK cells were depleted. Thus, NK cells operate in both induction and effector phases of the disease. IFN-\u03b3 was produced by neonatal NK cells in vivo, and it may be important in neonatal AOD. Indeed, ovaries with neonatal AOD expressed high levels of IFN-\u03b3 and TNF-\u03b1 which correlated with disease severity, and the disease was inhibited by IFN-\u03b3 or TNF-\u03b1 Ab. Importantly, disease was enhanced by recombinant IFN-\u03b3, and treatment of T cell donors with IFN-\u03b3 Ab also significantly reduced adoptive transfer of neonatal AOD. Finally, neonatal AOD was ameliorated in mice deficient in Fc\u03b3RIII and was enhanced in Fc\u03b3RIIB-deficient mice. We conclude that neonatal NK cells promote pathogenic T cell response at multiple stages during neonatal autoimmune disease pathogenesis. Also operative in neonatal AOD are other mediators of the innate system, including proinflammatory cytokines and Fc\u03b3RIII signaling.<\/jats:p>","DOI":"10.4049\/jimmunol.173.2.1051","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:37:22Z","timestamp":1398022642000},"page":"1051-1058","source":"Crossref","is-referenced-by-count":23,"title":["Requirements of NK Cells and Proinflammatory Cytokines in T Cell-Dependent Neonatal Autoimmune Ovarian Disease Triggered by Immune Complex"],"prefix":"10.1093","volume":"173","author":[{"given":"Yulius Y","family":"Setiady","sequence":"first","affiliation":[{"name":"Departments of Pathology , Charlottesville, VA 22908"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patcharin","family":"Pramoonjago","sequence":"additional","affiliation":[{"name":"Departments of Pathology , Charlottesville, VA 22908"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth S K","family":"Tung","sequence":"additional","affiliation":[{"name":"Departments of Pathology , Charlottesville, VA 22908"},{"name":"Microbiology, University of Virginia , Charlottesville, VA 22908"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,7,15]]},"reference":[{"key":"2026020212085226800_R1","first-page":"385","volume-title":"Semin. 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