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Alteration of liver‐infiltrated and peripheral blood double‐negative T‐cells in primary biliary cholangitis
Author(s) -
Li Shu X.,
Lv Ting T.,
Zhang Chun P.,
Wang Tian Q.,
Tian Dan,
Sun Guang Y.,
Wang Yan,
Zhao Xin Y.,
Duan Wei J.,
Chen Sha,
Li Min,
Ma Hong,
Kong Yuan Y.,
You Hong,
Ou Xiao J.,
Chen Guang Y.,
Su Jian R.,
Zhang Dong,
Jia Ji D.
Publication year - 2019
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.14136
Subject(s) - ursodeoxycholic acid , cytotoxic t cell , perforin , cd8 , immune system , t cell , pathogenesis , biology , interleukin 21 , immunology , medicine , in vitro , biochemistry
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.