{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:53:11Z","timestamp":1780105991969,"version":"3.54.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"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":[[2017,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Th cells sensitized against autoantigens acquire pathogenicity following two sequential events, namely activation by their target Ag and a process named \u201clicensing.\u201d In this study, we analyzed these processes in a transgenic mouse system in which TCR-transgenic Th cells specific to hen egg lysozyme (HEL) are adoptively transferred to recipients and induce inflammation in eyes expressing HEL. Our data show that the notion that the lung is the organ where \u201clicensing\u201d for pathogenicity takes place is based on biased data collected with cells injected i.v., a route in which most transferred cells enter via the lung. Thus, we found that when donor cells were activated in vitro and injected intraperitoneally, or were activated in vivo, they migrated simultaneously to the lung, spleen, and other tested organs. In all, tested organs donor cells undergo \u201clicensing\u201d for pathogenicity, consisting of vigorous increase in number and changes in expression levels of inflammation-related genes, monitored by both flow cytometry and microarray analysis. After reaching peak numbers, around day 3, the \u201clicensed\u201d donor cells migrate to the circulation and initiate inflammation in the HEL-expressing recipient eyes. Importantly, the kinetics of increase in number and of changes in gene expression by the donor cells were similar in lung, spleen, and other tested organs of the recipient mice. Furthermore, the total numbers of donor cells in the spleen at their peaks were 10- to 100-fold larger in the spleen than in the lung, contradicting the notion that the lung is the organ where \u201clicensing\u201d takes place.<\/jats:p>","DOI":"10.4049\/jimmunol.1502108","type":"journal-article","created":{"date-parts":[[2016,12,17]],"date-time":"2016-12-17T01:56:29Z","timestamp":1481939789000},"page":"681-690","source":"Crossref","is-referenced-by-count":10,"title":["Shedding New Light on the Process of \u201cLicensing\u201d for Pathogenicity by Th Lymphocytes"],"prefix":"10.1093","volume":"198","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8151-4051","authenticated-orcid":false,"given":"Cuiyan","family":"Tan","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, National Eye Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6254-7429","authenticated-orcid":false,"given":"Wambui S","family":"Wandu","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Eye Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-5314","authenticated-orcid":false,"given":"R Steven","family":"Lee","sequence":"additional","affiliation":[{"name":"Genetic Engineering Core, National Eye Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3322-3492","authenticated-orcid":false,"given":"Samuel H","family":"Hinshaw","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Eye Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis M","family":"Klinman","sequence":"additional","affiliation":[{"name":"Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health , Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2959-911X","authenticated-orcid":false,"given":"Eric","family":"Wawrousek","sequence":"additional","affiliation":[{"name":"Genetic Engineering Core, National Eye Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igal","family":"Gery","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Eye Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,1,15]]},"reference":[{"key":"2025030614593008200_r1","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/nri3095","article-title":"TLR-dependent T cell activation in autoimmunity","volume":"11","author":"Mills","year":"2011","journal-title":"Nat. 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