Predominant T-helper 1 cytokine profile of hepatitis B virus nucleocapsid-specific T cells in acute self-limited hepatitis B

Penna, Amalia; Prete, Gianfranco Del; Cavalli, A.; Bertoletti, Antonio; D’Elios, Mario Milco; Sorrentino, Rosa; D’Amato, Mauro; Boni, Carolina; Pilli, Massimo; Fiaccadori, F; Ferrari, Carlo

doi:10.1002/hep.510250438

Cited by 182 publications

(123 citation statements)

References 41 publications

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“…Experiments in HBV transgenic mice have provided evidence for the roles of IFN-␥ and TNF-␣ in the antiviral response to HBV (5,17). In humans a predominance of Th0 cells was detected in the liver, thus favoring the persistence of the virus (55,56). In contrast to what was observed during chronic hepatitis, a strong IFN-␥ production by Th1 cells in the peripheral blood was detected following antigenic stimulation of PBMC from acutely infected patients (57).…”

Section: Discussionmentioning

confidence: 87%

Multiepitopic HLA-A*0201-Restricted Immune Response Against Hepatitis B Surface Antigen After DNA-Based Immunization

Loirat

Lemonnier

Michel

2000

The Journal of Immunology

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CTL together with anti-envelope Abs represent major effectors for viral clearance during hepatitis B virus (HBV) infection. The induction of strong cytotoxic and Ab responses against the envelope proteins after DNA-based immunization has been proposed as a promising therapeutic approach to mediate viral clearance in chronically infected patients. Here, we studied the CTL responses against previously described hepatitis B surface Ag (HBsAg)-HLA-A*0201-restricted epitopes after DNA-based immunization in HLA-A*0201 transgenic mice. The animal model used was Human Human Db (HHD) mice, which are deficient for mouse MHC class I molecules (β2-microglobulin−/− Db−/−) and transgenic for a chimeric HLA-A*0201/Db molecule covalently bound to the human β2-microglobulin (HHD+/+). Immunization of these mice with a DNA vector encoding the small and the middle HBV envelope proteins carrying HBsAg induced CTL responses against several epitopes in each animal. This study performed on a large number of animals described dominant epitopes with specific CTL induced in all animals and others with a weaker frequency of recognition. These results confirmed the relevance of the HHD transgenic mouse model in the assessment of vaccine constructs for human use. Moreover, genetic immunization of HLA-A2 transgenic mice generates IFN-γ-secreting CD8+ T lymphocytes specific for endogenously processed peptides and with recognition specificities similar to those described during self-limited infection in humans. This suggests that responses induced by DNA immunization could have the same immune potential as those developing during natural HBV infection in human patients.

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Section: Discussionmentioning

confidence: 87%

Multiepitopic HLA-A*0201-Restricted Immune Response Against Hepatitis B Surface Antigen After DNA-Based Immunization

Loirat

Lemonnier

Michel

2000

The Journal of Immunology

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“…In acute HBV infection, Th1 cytokines are released, to promote a dominant cellular cytotoxic T-lymphocyte (CTL) immune response [25,26]. On the other hand, Th2 response is dominated the chronic HBV infection [27].…”

Section: Discussionmentioning

confidence: 99%

Association of Gene Polymorphisms and Serum Levels of IL-18 with the Susceptibility to Infection with Hepatitis B Virus

Hasan¹,

Naif²

2017

J Infect Dis Med

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Background: IL-18 gene polymorphisms is shown to be involved in various diseases. This study examines the influence of IL-18 gene polymorphism on the natural course of Hepatitis B Virus (HBV) infection together with the impact of serum levels in Iraqi population for the first time.Methods: A total of 55 patients and similar numbers of healthy controls were recruited in this study. Gene polymorphisms at positions -607C/A and -137G/C of IL-18 were examined using the allele-specific polymerase chain reaction (PCR). Serum levels of IL-18 were determined by an ELISA kit.Results: Three genotypes of IL-18-607C/A (rs1946518) were observed and distributed variably in both patients and controls: CC, CA, and AA with frequencies 41 (82%), 3 (6%), and 6 (12%), in patients and in 44 (88%), 5 (10%), and 1 (2%) in the controls, respectively. The homozygous -607AA mutant genotype, A and C allele frequencies were significantly higher (p=0.043) in patients than the healthy control group (A: 15% and 7%, p=0.04 and C: 85% and 93%, p=0.04, respectively) (OR=2.3445, 95%CI=0.9121-6.0269). The effect of treatment against HBV on genotype and allele frequencies compared with untreated patients revealed that CC and AA genotypes were significantly higher (p=0.04) in treated than untreated patients mirrored results obtained in patients and controls. Three genotypes of IL-18-137G/C (rs187238) were observed in both patients and healthy controls: GG, GC, and CC that appeared in 30 (60%), 18 (36%), and 2 (4%) of HBV infected patients and in 32 (64%), 16 (32%), and 2 (4%) of the control group, respectively. No significant genotype or alleles (G and C) frequencies observed between patients and controls (OR=0.863, 95%CI=0.4485-1.7516). Serum levels of IL-18 was found to be significantly higher in HBV-infected patients compared to the control group. IL-18 levels decreased significantly by various genotypes of both SNPs and this was consistently associated with the mutant genotypes of -137 SNP.Conclusion: IL-18-607AA mutant genotype and C and A alleles were significantly associated with a high risk to HBV infection in Iraqi population, however, the -137 genotypes had no clear impact on the disease and its role as a protective factor needs further investigation. In contrast, the downregulation of the circulating levels of IL-18 in patients was associated with the -137 and -607 mutant genotypes.

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“…IFN-␥ and IL-4 were quantitated by commercially available enzyme-linked immunosorbent assay (BioSource International Inc., Camarillo, CA, and Quantikine R & D Systems, Minneapolis, MN, respectively), as previously described. 9 HLA Typing and Determination of HLA Restriction. HLA typing was performed by LIPA assay kindly provided by Innogenetics, Zwijnaarde, Belgium, in accordance with the manufacturer' s instructions.…”

Section: Production Of Core-specific T-cell Clones and Olygoclonal T-mentioning

confidence: 99%

Conserved hepatitis C virus sequences are highly immunogenic for CD4+ T cells: Implications for vaccine development

et al. 1999

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The HLA class II-restricted T-cell response to hepatitis C virus (HCV) antigens is believed to influence the final outcome of hepatitis C, because it is vigorous in patients who recover from acute hepatitis C, but it is weak in those who develop a chronic infection. For this reason, exogenous stimulation of T-cell responses in chronic HCV infection may represent a strategy to cure patients with chronic hepatitis C by approximating the vigor of their T-cell reactivity to that of patients who succeed in recovering from hepatitis. It may also be a preventive approach to avoid spread of the virus by facilitating the development of a vigorous protective response at the very early stages of infection. T-cell-based vaccines composed of immunodominant, promiscuous, and conserved T-cell epitopes may represent a powerful tool to achieve optimal stimulation of the T-cell reactivity. To identify HLA class II-restricted T-cell epitopes useful for this purpose, 22 subjects with acute HCV infection were studied and followed for an average time of 29 months. Eight of them recovered from hepatitis, and 14 developed a chronic infection. Overlapping 20-mer peptides covering the entire core and NS4 antigens and a panel of peptides representing highly conserved regions of core, NS3, NS4, and NS5 were used. By direct peripheral blood T-cell stimulation and by finespecificity analysis of HCV-specific T-cell lines and clones, highly immunogenic T-cell epitopes were identified within core, NS3, and NS4. All these epitopes are immunodominant and highly conserved among the known HCV isolates. Moreover, they are promiscuous, because they can be presented to T cells by different HLA class II molecules. Immunodominance, sequence conservation, and promiscuity make these epitopes ideal components of preventive or therapeutic T-cell-based vaccines against HCV. (HEPATOL-OGY 1999;30:1088-1098.)The hepatitis C virus (HCV) is a RNA virus that can cause either acute self-limited infections or, more frequently, chronic liver cell injury leading to cirrhosis and hepatocellular carcinoma in a high proportion of cases. 1 The mechanisms responsible for persistence or viral clearance are still largely unknown. However, recent studies reported different patterns of proliferative T-cell response and cytokine production by antigen-specific CD4 ϩ T cells in patients with self-limited or chronically evolving HCV infection. [2][3][4] Patients with selflimited acute hepatitis show more vigorous peripheral blood proliferative T-cell responses to HCV proteins, predominantly sustained by Th1-like lymphocytes able to secrete proinflammatory cytokines (interferon gamma [IFN-␥] and interleukin-2 [IL-2]). Patients with chronic evolution of infection display weaker and less efficient proliferative T-cell responses suggesting that the intensity of the T-cell reactivity at the early stages of infection may be critical to limit the spread of the virus within the infected host and to keep viral replication under control. 2,3 In continuation of our previous studies suggestin...

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Predominant T-helper 1 cytokine profile of hepatitis B virus nucleocapsid-specific T cells in acute self-limited hepatitis B

Cited by 182 publications

References 41 publications

Multiepitopic HLA-A*0201-Restricted Immune Response Against Hepatitis B Surface Antigen After DNA-Based Immunization

Multiepitopic HLA-A*0201-Restricted Immune Response Against Hepatitis B Surface Antigen After DNA-Based Immunization

Association of Gene Polymorphisms and Serum Levels of IL-18 with the Susceptibility to Infection with Hepatitis B Virus

Conserved hepatitis C virus sequences are highly immunogenic for CD4+ T cells: Implications for vaccine development

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