Alteration of liver‐infiltrated and peripheral blood double‐negative T‐cells in primary biliary cholangitis. (10th June 2019) - Li, Shu X.
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.