Abstract
Primary biliary cirrhosis (PBC) is a type of organ-specific autoimmune disease in which immune tolerance is impaired by an unknown mechanism. We established a PBC animal model by injecting C57BL/6 mice with polyI:C to study activation-induced cell death (AICD) in CD4+ T lymphocytes and changes of apoptosis-associated molecules as a first step to understand the immune tolerance of PBC mice. Obvious inflammatory cell infiltration was observed in the portal area of the liver tissues in model mice and antimitochondrial antibodies (AMA) positive rate was 80%. The AICD level in both splenic and hepatic CD4+ T cells in the model group were all lower than those in controls, and in the model group the level for hepatic CD4+ T cells were significantly lower than that for splenic CD4+ T cells. Quantitative PCR revealed that FasL mRNA and TRAIL expression in CD4+ T cells in the model group decreased significantly compared with that in the control group. Western blots revealed that the expression of the anti-apoptotic protein FLIPL in the model group increased significantly with the FLIPL expression in hepatic CD4+ T cells significantly higher than that in splenic CD4+ T cells. There was a positive linear correlation between the number of infiltrated portal areas and relative expression of FLIPL in splenic CD4+ T cells in model group. There were no obvious changes for caspase-8 in either group. These results show that the anti-apoptotic ability of CD4+ T lymphocytes play an important role in immune tolerance in the PBC mouse model, and elevated FLIPL expression may enhance this ability. The inhibition of FasL and TRAIL expression may also help enhance this anti-apoptotic ability in CD4+ T lymphocytes and contribute to the aggravation of portal area inflammation.
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Acknowledgments
We thank Dr. Hongyu Yu and Lingzhen Zhang for technical assistance. This research was supported by National High-tech R&D Program (863 Program), code no.: 2006AA02Z496, Subject: Early diagnosis and immune tolerance reconstruction of autoimmune diseases; and funds for Excellent Department Leader, Science and Technology Commission of Shanghai Municipality,code no.: 07XD14013, Subject: The role of Toll-like receptors in primary biliary cirrhosis and atherosclerosis.
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T. Jiang, Z. Han and S. Chen have contributed equally to this work.
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Jiang, T., Han, Z., Chen, S. et al. Resistance to activation-induced cell death and elevated FLIPL expression of CD4+ T cells in a polyI:C-induced primary biliary cirrhosis mouse model. Clin Exp Med 9, 269–276 (2009). https://doi.org/10.1007/s10238-009-0052-2
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DOI: https://doi.org/10.1007/s10238-009-0052-2