Analysis of a Successful Immune Response against Hepatitis C Virus

Abstract

To investigate the type of immunity responsible for resolution of hepatitis C virus (HCV) infection, we monitored antibody and intrahepatic cytotoxic T lymphocyte (CTL) responses during acute (<20 weeks) infection in chimpanzees. Two animals who terminated infection made strong CTL but poor antibody responses. In both resolvers, CTL targeted at least six viral regions. In contrast, animals developing chronic hepatitis generated weaker acute CTL responses. Extensive analysis of the fine specificity of the CTL in one resolver revealed nine peptide epitopes and restriction by all six MHC class I allotypes. Every specificity shown during acute hepatitis persisted in normal liver tissue more than 1 yr after resolution. These results suggest that CD8+CTL are better correlated with protection against HCV infection than antibodies.

Cellular immune responses against hepatitis C virus: the evidence base 2002

“…• Clearance of acute infection in both man and in chimpanzee models is accompanied by strong CD4 + and CD8 + T cell responses against numerous HCV derived antigens [11,[13][14][15][16].…”

An analysis of tumor necrosis factor α gene polymorphisms and haplotypes with natural clearance of hepatitis C virus infection

“…A broad, vigorous cytotoxic T lymphocyte (CTL) response correlated with viral clearance in a study of six chimpanzees. 3 Similarly, studies in humans have shown that a strong, polyclonal CTL response is associated with viral clearance. 4 It is plausible that the vigor of the immune response is determined, at least in part, by host genetic factors.…”

Subversion of effector CD8+ T cell differentiation in acute hepatitis C virus infection: exploring the immunological mechanisms

“…Recent studies in humans and in the chimpanzee model indicate that the promptness of both T helper cell and CTL responses after HCV exposure seem to be criti- cal factors in determining the outcome of acute infection, i.e. recovery versus viral persistence [21][22][23][24][25][26][27][28][29][30][31]. Moreover, these data demonstrate that CTL, despite being considerably expanded and expressing a memory effector membrane phenotype (CCR7 -) [30,32,33], are functionally inadequate to fight HCV in a multitude of acutely infected people undergoing a state of long-lasting liver immunopathology [21][22][23][24][25][26][27][28][29][30][31].…”