Increased bcl-2 expression in lymphocytes and its association with hepatocellular damage in patients with autoimmune hepatitis

The proto-oncogene product bcl-2 is known to inhibit apoptotic cell death, and its dysregulation might play a critical role in the development of auto immune disease. To elucidate the role of bcl-2 in autoimmune hepatitis (AIH ), its expression in peripheral blood mononuclear cells (PBMC) and in liver -infiltrating lymphocytes (LIL) was investigated. Increased bcl-2 expressio n in PBMC was found in AIH patients compared with that in chronic hepatitis C (CHC) patients and in healthy controls. The level of bcl-2 expression si gnificantly correlated with serum ALT level. Further analysis showed that C D4(+) T cells are enriched in bcl-2-expressing PBMC. To characterize the Th 1/Th2 profile of bcl-2-expressing CD4(+) T cells, intracellular interferon- gamma (IFN-gamma) and IL-4 were analysed. The results revealed that most of the bcl-2-expressing cells were found to be IFN-gamma-secreting Th1 cells. In three patients for whom their clinical courses could be followed, bcl-2 expression was decreased after the initiation of immunosuppressive therapy with corticosteroids. However, the level of IFN-gamma(+) cells was not alt ered. Immunohistochemical analysis also showed that large amounts of bcl-2( +) cells were observed in periportal area in the liver. In conclusion, bcl- 2-expressing cells were shown to be increased in peripheral blood and liver in AIH and the bcl-2 product was expressed mainly in CD4(+) Th1-type cells , suggesting that these cells might promote the cellular immune response an d contribute to the development of hepatitis and hepatocellular damage in A IH.