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


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-? 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.

SUBMITTER: Lin HH 

PROVIDER: S-EPMC5337949 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Lin Han-Huei HH   Gutenberg Angelika A   Chen Tzu-Yu TY   Tsai Nu-Man NM   Lee Chia-Jung CJ   Cheng Yu-Che YC   Cheng Wen-Hui WH   Tzou Ywh-Min YM   Caturegli Patrizio P   Tzou Shey-Cherng SC  

Scientific reports 20170306


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  ...[more]

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