|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1994 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1993 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1992 : ¥700,000 (Direct Cost : ¥700,000)
In order to clarify the mechanism of liver injuries in chronic hepatitis, type C,we investigated immunopathological findings of hepatitis C virus (HCV) and cellular immune responses in liver biopsy specimens. An immunohistochemical method using anti-HCV core antigen (anti-HCc : anti-CP-9) and in situ hybridization technique using T-T dimerized oligo cDNA probes were applied. Cellular immune responses in liver tissues were observed by indirect immunoperoxidase method using anti-CD8, anti-CDllb, anti-CD4, anti-CD22 and anti-CD57 for the subpopulation of lymphocytes and T cell subsets. Anti-ABC,anti-DR,anti-DP,and anti-DQ were studies for HLA antigens. Anti-ICAM-1, anti-VCAM-1 and anti-LFA-1 were used for detection of adhesion molecules. Expression of FasAg on hepatocytes was also studied by immunoperoxidase method usingmouse monoclonal antibodies secreted by B cell hybridomas (clone ZB4 and UB2).
In most patients, liver cells with HCcAg and /or HCV-RNA were present in small mumbers and sporadically, but lobular distribution of HCV-positive hepatocytes was observed in some patients. Numerous Tlymphocytes were present immunohistochemically in the liver of patients with chronic active hepatitis, and particularly, numerous OKT8 (+), llb (-1) and LFA-1 (+) CTL infiltrated in areas of piecemeal necrosis and focal necrosis. On surface of hepatocytes in these areas, HLA-class 1 and ICAM-1 antigens were membranously expressed. FasAg was also observed diffusely on hepatocytes throughout lobules in most patients with chronic active hepatitis. These findings suggest liver cell injuries in chronic hepatitis C,may be caused by CD8+CTL recognizing HCV and HLA-class 1.