DEFECT OF CELL-MEDIATED IMMUNE-RESPONSE AGAINST HEPATITIS-B VIRUS - AN INDICATION FOR PATHOGENESIS OF HEPATITIS-B-VIRUS-ASSOCIATED MEMBRANOUS NEPHROPATHY

To elucidate the questions of why not all patients with hepatitis B vi rus (HBV) infection develop HBV membranous nephropathy (HBVMN), we fir st measured serum HBe circulating immune complex (CIC) during the acut e nephrotic phase of HBVMN and in HBV carriers, We found that the leve l of HBe CIC was low in the HBVMN patients and absent either in HBsAg/HBeAg+ patients without HBVMN or HBsAg+/HBeAg- asymptomatic carriers, Second, we needed to characterize the cellular immune response to HBV in patients with HBVMN, However, lack of a suitable autologous effect or/target cell system makes a precise study of HBVMN pathogenesis diff icult. In the present study, we established a model system by using au tologous HBcAg-expressing Epstein-Barr-virus-immortalized lymphoblasto id cell lines (LCL) as stimulator/target cells, Both proliferative res ponse after stimulation with HBcAg and cytotoxic activity against auto logous HBcAg-expressing LCL of the peripheral blood T cells obtained f rom the HBVMN patients and HBsAg carriers could be measured, Using aut ologous HBcAg-expressing LCL as stimulator/target cells for the study of HBcAg-specific cytotoxic T lymphocytes. we found that HBVMN patient s had lower cytotoxic activity than did both HBV carriers and HBsAg-/H BsAb+, HBeAg-/HBeAb+ children, From the in vitro cytokine production s tudy of peripheral blood T cells after stimulation with HBcAg, we foun d that T-helper-cell-1-related IL-2 and IFN-gamma productions were ver y low in HBVMN patients but T-helper-cell-2-related IL-10 production w as higher in HBsAg+/HBeAg+ patients with HBVMN than in those without H BVMN, Based on these findings, we conclude that HBVMN children seem to have an inadequate cellular immune response to HBcAg.