Modeling the T-helper cell response in acute and chronic hepatitis B virus infection using T-cell receptor transgenic mice

Chen, M; Sällberg, Matti; Thung, S N; Hughes, Janice; Jones, Joyce; Milich, David R.

doi:10.1016/s0166-3542(01)00174-7

Cited by 8 publications

(5 citation statements)

References 20 publications

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“…Our findings indicate that CHB patients have T-cell failure. The same finding has also been demonstrated previously, namely, that the chronicity of HBV infection is caused by a deficiency in cellular immune function [16][17][18][19][20] , and hepatocyte damage is mainly caused by immunological injur y [21][22][23][24][25][26][27][28][29] . However, the mechanism has not been defined [5] .…”

Section: Figuresupporting

confidence: 77%

“…Therefore, immune elimination of infected cells can lead to the termination of infection when it is efficient, or to a persistent necroinflammatory disease when it is not [47] . Destruction of infected cells, however, is not the only mechanism implicated in the elimination of intracellular virus, as demonstrated by studies carried out in animal models of HBV infection and in human hepatitis B, which demonstrate the importance of cytokine-mediated, noncytolytic mechanisms of anti-viral protection [20][21][22][23][24][25][26][27][28][29][30][31] .…”

Section: Figurementioning

confidence: 99%

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Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B

You¹,

Sriplung²,

Geater³

et al. 2008

WJG

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AIM:To investigate peripheral T-lymphocyte subpopulation profile and its correlation with hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB). METHODS:Distribution of T-lymphocyte subpopulations in peripheral blood was measured by flow cytometry in 206 CHB patients. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time polymerase chain reaction (PCR). The relationship between HBV replication and variation in peripheral T-cell subsets was analyzed. showed a similar pattern of these parameters was significantly associated with high viral load, presence of serum hepatitis B e antigen (HBeAg) expression, liver disease severity, history of maternal HBV infection, and young age at HBV infection, all with P < 0.01. There was a significant linear relationship between viral load and these parameters of T-lymphocyte subpopulations (linear trend test P < 0.001). There was a negative correlation b e t w e e n t h e l e ve l s o f C D 3 + a n d C D 4 + c e l l s a n d CD4 + /CD8 + ratio and serum level of viral load in CHB patients (r = -0.68, -0.65 and -0.75, all P < 0.0001), and a positive correlation between CD8 + cells and viral load (r = 0.70, P < 0.0001). There was a significant decreasing trend in CD3 + and CD4 + cells and CD4 + /CD8 + ratio with increasing severity of hepatocyte damage and decreasing age at HBV infection (linear trend test P < 0.01). In multiple regression (after adjustment for age at HBV infection, maternal HBV infection status and hepatocyte damage severity) log copies of HBV DNA maintained a highly significant predictive coefficient on T-lymphocyte subpopulations, and was the strongest predictor of variation in CD3 + , CD4 + , CD8 + cells and CD4 + /CD8 + ratio. However, the effect of HBeAg was not significant. RESULTS CONCLUSION:T-lymphocyte failure was significantly associated with viral replication level. The substantial linear dose-response relationship and strong independent predictive effect of viral load on T-lymphocyte subpopulations suggests the possibility of a causal relationship between them, and indicates the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients.

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Section: Figuresupporting

confidence: 77%

Section: Figurementioning

confidence: 99%

Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B

You¹,

Sriplung²,

Geater³

et al. 2008

WJG

View full text Add to dashboard Cite

show abstract

“…Recently, the results have been reported by Tian et al [22] that CD4 + and CD8 + T cells decreased in both 33 CHB patients and 21 asymptomatic HBV carriers. Thus, most evidence has come from research in experimental animals [23][24][25] and in CHB patients [26][27][28][29][30] . Our results reveal that T-cell impairment was significantly associated with viral replication level.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus DNA is more powerful than HBeAg in predicting peripheral T-lymphocyte subpopulations in chronic HBV-infected individuals with normal liver function tests

You¹,

Sriplung²,

Geater³

et al. 2008

WJG

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AIM:To investigate the peripheral T-lymphocyte subpopulation profile, and its correlations with hepatitis B virus (HBV) replication level in chronic HBV-infected (CHI) individuals with normal liver function tests (LFTs). METHODS: Frequencies of T-lymphocyte subpopulations in peripheral blood were measured by flow cytometry in 216 CHI individuals. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time PCR. Information of age at HBV infection, and maternal HBV infection status was collected. ANOVA linear trend test and linear regression were used in statistical analysis. RESULTS: CHI individuals had significantly decreased relative frequencies of CD3 + , CD4 + subpopulations and CD4 + /CD8 + ratio, and increased CD8 + subset percentage compared with uninfected individuals (all P < 0.001). There was a significant linear relationship between the load of HBV DNA and the parameters of T-lymphocyte subpopulations (ANOVA linear trend test P < 0.01). The parameters were also significantly worse among individuals whose mothers were known to be HBV carriers, and those having gained infection before the age of 8 years. In multiple regressions, after adjustment for age at HBV infection and status of maternal HBV infection, log copies of HBV DNA maintained its highly significant predictive coefficient on T-lymphocyte subpopulations, whereas the effect of HBeAg was not significant. CONCLUSION: HBV DNA correlates with modification in the relative T-lymphocyte subpopulation frequencies. High viral load is more powerful than HBeAg in predicting the impaired balance of T-cell subsets.

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“…However, the results of previous studies are controversial results [28][29][30][31][32] . The fact that chronic hepatitis B represents a dynamic disease state may explain such divergent results.…”

mentioning

confidence: 96%

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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Modeling the T-helper cell response in acute and chronic hepatitis B virus infection using T-cell receptor transgenic mice

Cited by 8 publications

References 20 publications

Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B

Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B

Hepatitis B virus DNA is more powerful than HBeAg in predicting peripheral T-lymphocyte subpopulations in chronic HBV-infected individuals with normal liver function tests

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

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