Immune response to a hepatitis C virus nonstructural protein in chronic hepatitis C virus infection

The immune responses to a hepatitis C virus nonstructural protein (T3Ag) overlapping with the C100-3 antigen were examined in three groups of patients with chronic non-A, non-B hepatitis. Group I included 20 cases positive for both anti-C100-3 and the second-generation anti-HCV test (anti-HCV-II); Group II, five cases with anti-C100-3(-)/anti-HCV-II(+); and Group III, seven cases negative for both tests. HCV RNA was detectable in 20 (100%), 4 (80%) and 0 (0%) patients in each group, respectively. Proliferative responses of peripheral blood mononuclear cells to T3Ag were present in 16 (80%), 3 (60%) and 0 (0%) cases in each group, respectively (p<0.05). Removal of CD8+ T cells from peripheral blood mononuclear cells resulted in a conversion of unresponsiveness to significant proliferation to T3Ag in the remaining cases in groups I and II, but not in group III. This change paralleled the antigen-induced production of interferon-γ and interleukin-2, but not interleukin-4. The removal also enhanced the T3Ag-stimulated anti-C100-3 antibody production from cultured peripheral blood mononuclear cells in group II patients. These results indicate that the T3Ag-specific type 1 T helper cells play an important role in regulating anti-C100-3 antibody secretion in hepatitis C patients.