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In Situ Activation of Pituitary-Infiltrating T Lymphocytes in Autoimmune Hypophysitis
- 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.
- Subjects :
- 0301 basic medicine
Pathology
medicine.medical_specialty
Pituitary gland
T-Lymphocytes
T cell
CD3
Lymphocyte Activation
Article
Immunophenotyping
Flow cytometry
Mice
03 medical and health sciences
0302 clinical medicine
Parenchyma
medicine
Animals
Autoimmune Hypophysitis
Lymphocyte Count
Cell Proliferation
B-Lymphocytes
Multidisciplinary
medicine.diagnostic_test
biology
business.industry
Dendritic Cells
medicine.disease
Immunohistochemistry
3. Good health
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Pituitary Gland
030220 oncology & carcinogenesis
biology.protein
Autoimmune hypophysitis
Cytokines
Female
Inflammation Mediators
business
Infiltration (medical)
Biomarkers
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....9dfbda208f95b17881808d49c07c4ec8
- Full Text :
- https://doi.org/10.1038/srep43492