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

Han Huei Lin, Angelika Gutenberg, Tzu Yu Chen, Nu Man Tsai, Chia Jung Lee, Yu Che Cheng, Wen Hui Cheng, Ywh Min Tzou, Patrizio Caturegli, Shey Cherng Tzou

Research output: Contribution to journalArticlepeer-review

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-Î 3 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.

Original languageEnglish (US)
Article number43492
JournalScientific reports
Volume7
DOIs
StatePublished - Mar 6 2017

ASJC Scopus subject areas

  • General

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