B7 BB-1 EXPRESSION AND HEPATITIS ACTIVITY IN LIVER-TISSUES OF PATIENTS WITH CHRONIC HEPATITIS-C/

Cytotoxic T lymphocytes (CTL) are closely related to the mechanism of liver injury in chronic viral hepatitis. Recently, it has been suggest ed that antigen-specific T cell activation requires both presentation of antigen by major histocompatibility complex (MHC) molecules and the delivery of costimulatory signals. Such signals are provided by B7/BB -1, one of the most important accessory molecules, sufficient for caus ing antigen-specific MHC-restricted T cell activation. To evaluate the role of B7/BB-1 in chronic hepatitis C, we immunohistochemically stud ied its expression in liver tissues obtained from 61 patients with hep atitis C virus (HCV) infection and compared them based on hepatitis ac tivity. In HCV-infected liver, B7/BB-1 was strongly expressed in the c ytoplasm of hepatocytes. B7/BB-1-positive cells accompanied liver-infi ltrating lymphocytes and were mainly detected in the periportal region . B7/BB-1 expression was closely correlated with the activity of viral hepatitis as evaluated from scores of periportal or intralobular infl ammation and necrosis, or serum alanine transferase (ALT) levels. Furt her study by immunostaining with anti-HCV core and anti-human leukocyt e antigen (HLA) class I antibody showed B7/BB-1 positive cells near HC V core antigen- and HLA class I-positive cells, with B7/BB-1-positive cells mostly included among HLA class I-positive cells. These findings suggested that B7/BB-1 expression by hepatocytes may be induced by HC V infection and may trigger generation and activation of CTL, which ma y cause damage to HCV-infected HLA class I-expressing hepatocytes.