Abstract: Background: Some populations of extrathymic T cells including natural killer T (NKT) cells are involved in autoimmune diseases. In particular, a deficiency of NKT cells has been implicated in human systemic sclerosis. Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the selective destruction of intrahepatic small bile ducts and the formation of granulomas. It is generally believed that cellular immune mechanisms, particularly T cells, cause the bile duct damage in PBC.
Methods: In this study, to investigate the unique population of extrathymic T cells in PBC, we examined the T cell receptor (TCR) Vα24-JαQ gene and CD57 + CD3 + cells corresponding to the major genotype and one of the phenotypes of NKT cells, respectively.
Results: By reverse transcription-polymerase chain reaction (RT-PCR), amplicons of the Vα24-JαQ gene fragment in liver tissues of PBC were found to be similar to those of control diseased livers, demonstrating that there was no distinct deficiency of Vα24-JαQ + NKT cells in PBC. Immunohistochemistry for CD57 and CD3 revealed the CD57 + CD3 + cells to be distributed in portal tracts and hepatic parenchyma in all cases studied, but the numbers of these cells were increased within portal tracts in PBC, in particular around injured interlobular bile ducts, compared to other diseased and normal livers.
Conclusion: This indicates that an immune disturbance induced by a selective reduction of Vα24-JαQ + NKT cells is unlikely to occur in PBC. Inversely, it can be postulated that auto aggressive CD57 + CD3 + NKT cells are recruited to regulate the altered immunity of the periductal microenvironment in PBC.