Alteration of liver-infiltrated and peripheral blood double-negative T-cells in primary biliary cholangitis

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.

Keywords: bile acid; double negative T-cells; lithocholic acid; primary biliary cholangitis.