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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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
Article number43492
JournalScientific reports
Volume7
DOIs
StatePublished - 6 Mar 2017

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