Inefficient Recognition of Autologous Viral Sequences by Intrahepatic Hepatitis C Virus-Specific Cytotoxic T Lymphocytes in Chronically Infected Subjects

Giuggio, Vicki M.; Bonkovsky, Herbert L.; Smith, J. MacLean; Rothman, Alan L.

doi:10.1006/viro.1998.9401

Cited by 18 publications

(13 citation statements)

References 25 publications

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“…Multivariate multiple regression analysis in our study demonstrated a partial independent effect of HBeAg and pre-core mutant infection on T-cell profile, which is supported by previous studies [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69] . It is well known that factors including HBeAg [53][54][55][56][57][58][59] and viral mutations [60][61][62][63][64][65][66][67][68][69] may contribute to the outcome and pathogenesis of HBV infection by inducing tolerance to specific T cells, reducing their potential to kill cells, inhibiting antigen processing and presentation, thereby decreasing the visibility of infected hepatocytes in the immune system.…”

supporting

confidence: 90%

“…It is well known that factors including HBeAg [53][54][55][56][57][58][59] and viral mutations [60][61][62][63][64][65][66][67][68][69] may contribute to the outcome and pathogenesis of HBV infection by inducing tolerance to specific T cells, reducing their potential to kill cells, inhibiting antigen processing and presentation, thereby decreasing the visibility of infected hepatocytes in the immune system. In addition, our results indicate that there was no significant difference of the proportion of T-cell subsets in patients at different ages of HBV infection and in patients of maternal HBV carrier status after adjustment for serum HBV load.…”

mentioning

confidence: 99%

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Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load

You¹,

Zhang²,

Zhang³

et al. 2009

WJG

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AIM:To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus (HBV) replication in different clinical stages of chronic HBV infection. METHODS:A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages: immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. Serum HBV DNA load was assessed by quantitative real-time polymerase chain reaction. RESULTS: CD8+ T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages (36.87 ± 7.58 vs 34.37 ± 9.07, 36.87 ± 7.58 vs 28.09 ± 5.64, P < 0.001). The peripheral blood in patients at the + T-cells were significantly increased in patients with a low HBV DNA load (37.45 ± 6.14, 33.33 ± 5.61, 31.58 ± 6.99 and 27.56 ± 5.49, P < 0.001). Multiple regression analysis displayed that log copies of HBV DNA still maintained its highly significant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3 + , CD4 + and CD8 + cells and CD4 + /CD8 + ratio after adjustment for age at HBV-infection, maternal HBV-infection status, presence of hepatitis B e antigen and HBV mutation.CONCLUSION: Differences in peripheral T-cell subpopulation profiles can be found in different clinical stages of chronic HBV infection. T-cell impairment is significantly associated with HBV load.

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supporting

confidence: 90%

mentioning

confidence: 99%

Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load

You¹,

Zhang²,

Zhang³

et al. 2009

WJG

View full text Add to dashboard Cite

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“…[21][22][23] Briefly, liver biopsy fragments were incubated in culture medium in the presence of 1 g/mL anti-CD3 and 100 U/mL recombinant human IL-2. When there was significant growth of lymphocytes extending out from the tissue (generally 2-4 weeks), the cells were restimulated at a density of approximately 2.5 ϫ 10 6 cells/mL with anti-CD3 and recombinant human IL-2 in the presence of allogeneic ␥-irradiated PBMCs.…”

Section: Methodsmentioning

confidence: 99%

“…Percent specific target cell lysis was calculated as described. [21][22][23] NA Assays. Pseudotype vesicular stomatitis virus (VSV) virions were prepared by phenotypic mixing of HCV chimeric envelope glycoproteins (E1-G or E2-G) and incorporation into the VSVts045 temperature-sensitive mutant as described.…”

Section: Methodsmentioning

confidence: 99%

Associations among clinical, immunological, and viral quasispecies measurements in advanced chronic hepatitis C†

et al. 2005

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The relationships among host immune and viral factors and the severity of liver disease due to hepatitis C virus (HCV) are poorly understood. Previous studies have focused on individual components of the immune response to HCV, often in relatively small numbers of patients. We measured HCV-specific lymphoproliferation (LP), intrahepatic cytotoxic T lymphocyte (CTL), and neutralizing antibody (NA) responses and HCV quasispecies (QS) diversity and complexity in a large cohort of subjects with advanced liver fibrosis (Ishak stages 3-6) on entry into the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. We correlated LP, CTL, NA, and QS results with clinical characteristics, including serum alanine aminotransferase (ALT), HCV RNA level, HCV genotype, and hepatic histopathology. LP, CTL, and NA responses were detected in 37%, 22%, and 22% of subjects tested, respectively. The only association that was statistically significant was higher mean serum ALT values in patients with detectable HCV-specific CTL responses (P ‫؍‬ .03). In conclusion, immune responses to HCV and viral diversity showed little relationship to clinical or histological features at a single time point in this selected population of patients with advanced chronic hepatitis C for whom prior interferon treatment had failed. (HEPATOLOGY 2005;41:617-625.)

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“…While such T-cell responses could still correlate with clinical outcomes, some observations in HCV immune pathogenesis may need to be reexamined in consideration of the nature of circulating HCV subtypes and target antigens used to study the T-cell response. Further studies are also needed to examine if T cells homing to the liver are more specific for the circulating virus or not (20).…”

Section: Vol 79 2005mentioning

confidence: 99%

Strain-Specific T-Cell Suppression and Protective Immunity in Patients with Chronic Hepatitis C Virus Infection

Sugimoto

Kaplan

Ikeda

et al. 2005

J Virol

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Hepatitis C virus (HCV) frequently persists with an apparently ineffective antiviral T-cell response. We hypothesized that some patients may be exposed to multiple HCV subtypes and that strain-specific T cells could contribute to the viral dynamics in this setting. To test this hypothesis, CD4 T-cell responses to three genotype 1a-derived HCV antigens and HCV antibody serotype were examined in chronically HCV infected (genotypes 1a, 1b, 2, 3, and 4) and spontaneously HCV recovered subjects. Consistent with multiple HCV exposure, 63% of patients infected with genotypes 2 to 4 (genotypes 2-4) and 36% of those infected with genotype 1b displayed CD4 T-cell responses to 1a-derived HCV antigens, while 29% of genotype 2-4-infected patients showed serotype responses to genotype 1. Detection of 1a-specific T cells in patients without active 1a infection suggested prior self-limited 1a infection with T-cell-mediated protection from 1a but not from non-1a viruses. Remarkably, CD4 T-cell responses to 1a-derived HCV antigens were weakest in patients with homologous 1a infection and greater in non-1a-infected patients: proportions of patients responding were 19% (1a), 36% (1b), and 63% (2-4) (P ‫؍‬ 0.0006). Increased 1a-specific CD4 T-cell responsiveness in non-1a-infected patients was not due to increased immunogenicity or cross-reactivity of non-1a viruses but directly related to sequence divergence. We conclude that the T-cell response to the circulating virus is either suppressed or not induced in a strain-specific manner in chronically HCV infected patients and that, despite their ability to clear one HCV strain, patients may be reinfected with a heterologous strain that can then persist. These findings provide new insights into host-virus interactions in HCV infection that have implications for vaccine development.

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Inefficient Recognition of Autologous Viral Sequences by Intrahepatic Hepatitis C Virus-Specific Cytotoxic T Lymphocytes in Chronically Infected Subjects

Cited by 18 publications

References 25 publications

Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load

Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load

Associations among clinical, immunological, and viral quasispecies measurements in advanced chronic hepatitis C†

Strain-Specific T-Cell Suppression and Protective Immunity in Patients with Chronic Hepatitis C Virus Infection

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