標題: In Situ Activation of Pituitary-Infiltrating T Lymphocytes in Autoimmune Hypophysitis
作者: Lin, Han-Huei
Gutenberg, Angelika
Chen, Tzu-Yu
Tsai, Nu-Man
Lee, Chia-Jung
Cheng, Yu-Che
Cheng, Wen-Hui
Tzou, Ywh-Min
Caturegli, Patrizio
Tzou, Shey-Cherng
生物科技學系
分子醫學與生物工程研究所
Department of Biological Science and Technology
Institute of Molecular Medicine and Bioengineering
公開日期: 6-Mar-2017
摘要: Autoimmune hypophysitis (AH) is a chronic inflammatory disease characterized by infiltration of T and B lymphocytes in the pituitary gland. 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-gamma and interleukin-17 upon stimulation in vitro. 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 in situ during AH, providing a previously unknown pathogenic mechanism and new avenues for treatment.
URI: http://dx.doi.org/10.1038/srep43492
http://hdl.handle.net/11536/133138
ISSN: 2045-2322
DOI: 10.1038/srep43492
期刊: SCIENTIFIC REPORTS
Volume: 7
起始頁: 0
結束頁: 0
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