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In Situ Activation of Pituitary-Infiltrating T Lymphocytes in Autoimmune Hypophysitis

Authors :
Tzu Yu Chen
Wen Hui Cheng
Patrizio Caturegli
Han Huei Lin
Ywh-Min Tzou
Yu Che Cheng
Shey Cherng Tzou
Chia-Jung Lee
Nu Man Tsai
Angelika Gutenberg
Source :
Scientific Reports
Publication Year :
2017
Publisher :
Springer Science and Business Media LLC, 2017.

Abstract

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-γ 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.

Details

ISSN :
20452322
Volume :
7
Database :
OpenAIRE
Journal :
Scientific Reports
Accession number :
edsair.doi.dedup.....9dfbda208f95b17881808d49c07c4ec8
Full Text :
https://doi.org/10.1038/srep43492