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Alteration of liver‐infiltrated and peripheral blood double‐negative T‐cells in primary biliary cholangitis
- Source :
- Liver International. 39:1755-1767
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Background & aims Double-negative (DN) T-cell is a unique regulatory T-cell, which is essential for maintaining immune system homoeostasis. However, the role of DN T-cells in the pathogenesis of primary biliary cholangitis (PBC) is still unknown. Methods We investigated the number and function of DN T-cells in peripheral blood and liver biopsy specimens of PBC patients. Results The number and frequency of DN T-cells significantly decreased in peripheral blood and liver tissue of PBC patients. Furthermore, the frequency of DN T-cells in PBC was negatively correlated with disease severity and positively correlated with ursodeoxycholic acid response. In vitro assays showed that perforin expression and the suppressive capability of DN T-cells on the proliferation of CD4+ and CD8+ T-cells were impaired in PBC. Finally, lithocholic acid, the most hydrophobic acid, could downregulate the proliferation and perforin expression of DN T-cells. Conclusions Decreased quantity and function of DN T-cells in PBC may result in the loss of immune regulations on effector CD4+ and cytotoxic CD8+ T-cells, and thereby may break the immune tolerance and promote the pathogenesis of PBC.
- Subjects :
- Adult
CD4-Positive T-Lymphocytes
Male
medicine.drug_class
CD8-Positive T-Lymphocytes
T-Lymphocytes, Regulatory
Immune tolerance
Pathogenesis
03 medical and health sciences
0302 clinical medicine
Immune system
Humans
Medicine
Cytotoxic T cell
Aged
Cell Proliferation
Hepatology
Bile acid
biology
medicine.diagnostic_test
Liver Cirrhosis, Biliary
business.industry
Ursodeoxycholic Acid
Middle Aged
digestive system diseases
Ursodeoxycholic acid
Liver
Perforin
Case-Control Studies
030220 oncology & carcinogenesis
Liver biopsy
Immunology
biology.protein
Female
030211 gastroenterology & hepatology
business
medicine.drug
Subjects
Details
- ISSN :
- 14783231 and 14783223
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Liver International
- Accession number :
- edsair.doi.dedup.....fef27e88f16ede91b34ab284e24c41e6