title: 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-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.
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu 30068, Taiwan.
authors.forename: Han-Huei
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, Johannes Gutenberg University, Mainz 55131, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Gutenberg
authors.affiliation: Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsin-Chu 30068, Taiwan.
authors.forename: Tzu-Yu
authors.initials: TY
authors.lastname: Chen
authors.affiliation: Department of Medical Technology and Biotechnology, School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
authors.forename: Nu-Man
authors.initials: NM
authors.lastname: Tsai
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu 30068, Taiwan.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsin-Chu 30068, Taiwan.
authors.forename: Yu-Che
authors.initials: YC
authors.lastname: Cheng
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu 30068, Taiwan.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Ywh-Min
authors.initials: YM
authors.lastname: Tzou
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Caturegli
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu 30068, Taiwan.|Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsin-Chu 30068, Taiwan.
authors.forename: Shey-Cherng
authors.initials: SC
authors.lastname: Tzou
mesh_terms: D000818:Animals; D000069281:Autoimmune Hypophysitis / Q000276:immunology* / Q000473:pathology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D010902:Pituitary Gland / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators