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Quantification of Hepatitis B Virus-specific T-cell Responses in HIV/HBV Co-infected Individuals
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Reported by Jules Levin Chang, Locarnini et al from Austarlia reported at the 11th RetrovirusConference on the immune effect of having HBV for HBV/HIV coinfected patients.
In HIV/HBV co-infected patients with persistent HBV replication receiving antiretroviral therapy (ART), immune restoration has been associated with an increased progression of liver disease, worsening hepatitis and severe liver failure in some individuals, while in others, ART is associated with the generation of HBV-specific immunity and HBeAg seroconversion. In order to better understand HBV immunopathogenesis in the setting of HIV infection, better methods are needed to study HBV-specific T cell immunity.
A peptide library to the entire genome of HBV (genotype A) was designed as 15-mers, overlapping by 11 amino acids allowing analysis of both CD4+ and CD8+ T-cell responses. An additional 150 15-mers were designed to areas of inter-genotype heterogeneity for genotypes B, C and D resulting in a total of 500 peptides. A panel of 21 9-mer and 10-mer peptides, previously defined as HLA-A2 restricted CTL epitopes were also generated. In HIV-infected patients, peptide pools to HIV env, gag, pol and accessory genes (obtained from the NIH reagent database) were analysed on the same blood sample. Using these peptides, in pools of up to 100, HBV-specific responses were assessed by ELISpot and/or intracellular cytokine staining (ICS) using antibodies to CD3, CD4, CD8, and interferon-g (IFN-g).
Background responses were initially evaluated using HBV-negative donors (n = 13). Blood was obtained from chronic carriers of HBV (n = 37) including patients treated with lamivudine (n = 23), and/or co-infected with HIV and treated with tenofovir or lamivudine (n = 14). Detection of spot forming cells (SFC) by ELISpot was far more frequent using peptide pools compared to previously defined HLA-A2 epitopes. Using ICS, HBV-specific CD8+IFN-g+T cells were detected more frequently (including percentage and number of positive peptide pools) in individuals taking anti-HBV therapy. Overall, HBV-specific CD4+IFN-g+ T cells were far less frequent than CD8+ IFN-g+ T cells.
There was a significant reduction in CD4+ IFN-g+ T cells in the setting of co-infection with HIV but no significant difference in the magnitude or breadth of CD8+ IFN-g+ T cells. HBV-specific responses were significantly lower than HIV-specific responses in all co-infected individuals.
The authorsconcluded that co-infection of HBV and HIV is primarily associated with a reduction of HBV-specific CD4+ T-cell responses with little effect on HBV-specific CD8+ T-cell responses.
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