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The role of cytotoxic T lymphocyte responses, restricted by human leukocyte antigen (HLA) class I alleles, is recognized as highly significant in the successful clearance of hepatitis C virus (HCV). The frequency of class I alleles in females inoculated with HCV genotype 1b from a single source was examined for an association with outcome. Class I typing was performed using polymerase chain reaction sequence-specific primers in 227 female subjects: 141 had chronic infection and 86 had viral clearance. Statistical analysis included 2 testing and multiple logistic regression analysis. A*03, B*27, and Cw*01 occurred more frequently in those with viral clearance (39.5%, 14%, and 9.3%, respectively) compared with those with chronic infection (19.1%, 2.1%, and 1.4%, respectively; P < .005). B*08 occurred more often in those with chronic infection compared with viral clearance (39.7% vs. H epatitis C virus (HCV) is a hepatotropic virus with a high rate of chronic infection. It is known that progression to cirrhosis and hepatocellular carcinoma may take up to 20 years in individuals who are chronically infected and thus represents a leading cause of hepatocellular morbidity and mortality. [1][2][3][4] To date, viral factors (e.g., genotype) and host factors (e.g., age of acquisition, male sex, and alcohol consumption) are known to alter both the natural history of the disease and treatment outcomes. 2,4-6 As yet, no in vivo models of infection are available in HCV infection, therefore the pathogenic mechanism of disease remains unclear. 19.8%; P ‫؍‬ .002). In combination with previously reported class II allele associations, overIn HCV infection, recognition and elimination of infected cells by cytotoxic T lymphocytes (CTLs) require the presentation of specific HCV antigens on the membrane of hepatocytes in the context of HLA-A, -B and -C antigens. In acute HCV infection, animal models suggest that viral clearance appears to be dependent on an intrahepatic CTL response directed against multiple HCV antigens restricted by several class I molecules. 7 Human studies on peripheral blood similarly report that viral clearance is associated with a strong initial HCV-specific

The factors that determine persistence or clearance of hepatitis C virus (HCV) infection are poorly understood. The CD4 T cell responses to the HCV core protein were examined in a cohort of women infected with a single genotype of HCV. CD4 T cells from HCV-infected patients secreted interferon (IFN)-gamma in response to peptides from 4 immunodominant regions of the core protein, and these responses were stronger in persistently infected women. Interleukin (IL)-10 was also produced by CD4 T cells from HCV-infected subjects in response to the same core peptides. Furthermore, HCV core-specific CD4 T cell clones secreted either IFN-gamma or IL-10 but not IL-4. These findings demonstrate that T helper type 1 and regulatory T cells are induced against the same epitopes on the core protein during HCV infection.

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