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The mechanisms through which infiltrating lymphocytes cause disease remain unknown. Using a mouse model of AH we assessed whether T lymphocytes undergo activation in the pituitary gland. Infiltrating T cells co-localized with dendritic cells in the pituitary and produced increased levels of interferon-\u03b3 and interleukin-17 upon stimulation i<jats:italic>n vitro<\/jats:italic>. Assessing proliferation of CD3- and B220-postive lymphocytes by double immunohistochemistry (PCNA-staining) and flow cytometry (BrdU incorporation) revealed that a discrete proportion of infiltrating T cells and B cells underwent proliferation within the pituitary parenchyma. This proliferation persisted into the late disease stage (day 56 post-immunization), indicating the presence of a continuous generation of autoreactive T and B cells within the pituitary gland. T cell proliferation in the pituitary was confirmed in patients affected by autoimmune hypophysitis. In conclusion, we show that pituitary-infiltrating lymphocytes proliferate<jats:italic>in situ<\/jats:italic>during AH, providing a previously unknown pathogenic mechanism and new avenues for treatment.<\/jats:p>","DOI":"10.1038\/srep43492","type":"journal-article","created":{"date-parts":[[2017,3,6]],"date-time":"2017-03-06T10:45:48Z","timestamp":1488797148000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["In Situ Activation of Pituitary-Infiltrating T Lymphocytes in Autoimmune Hypophysitis"],"prefix":"10.1038","volume":"7","author":[{"given":"Han-Huei","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelika","family":"Gutenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu-Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nu-Man","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Jung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Che","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Hui","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ywh-Min","family":"Tzou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizio","family":"Caturegli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shey-Cherng","family":"Tzou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,3,6]]},"reference":[{"key":"BFsrep43492_CR1","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1210\/jc.2007-0808","volume":"92","author":"P Caturegli","year":"2007","unstructured":"Caturegli, P. 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