Z Gastroenterol 2014; 52 - P_5_22
DOI: 10.1055/s-0033-1361031

HIV-1 infection impairs frequency and functionality of HBV-specific CD4 T cells in patients with chronic hepatitis B

C Russo 2, C Dembek 1, F Geisler 3, A Umgelter 3, R Draenert 4, U Protzer 1, T Bauer 2
  • 1Helmholtz Zentrum/Technische Universitaet Muenchen, Institute of Virology, Munich, Germany
  • 2Helmholtz Zentrum/Technische Universitaet Muenchen, Clinical Cooperation Group 'Immune Monitoring', Munich, Germany
  • 3University Hospital Rechts der Isar, II. Medical Department, Munich, Germany
  • 4University Hospital München, IV. Medical Department, Munich, Germany

Globally about 10% of HIV-1-positive patients are chronically coinfected with HBV leading to an increased morbidity and mortality compared to patients with HBV monoinfection. We analyzed frequency and functionality of HBV- and HIV-specific CD4 and CD8 T cells in patients with HIV/HBV coinfection (n = 11) compared to HBV (n = 15) and HIV (n = 8) monoinfected patients. Peripheral blood mononuclear cells were isolated and analyzed for T-cell activation (CD40L), cytokine (IFN-γ, TNF-α, IL-2) and chemokine (MIP1-β) secretion ex vivo after overnight resting by flow cytometry-based assays.

In patients with HIV/HBV coinfection we observed a significant higher median frequency of HBV (core+S)-specific CD4 T cells (0.032%, range: 0.013 – 0.182%) compared to HBV monoinfected patients (0.015%, range: 0.007 – 0.300%; p = 0.043). In contrast, median frequency of HBV-specific CD8 T cells did not significantly differ between the cohorts. Patients with HIV/HBV coinfection showed a significantly higher proportion of monofunctional, predominantly IL-2-secreting HBV-specific CD4 T cells (0.016%, range: 0.000 – 0.160%) compared to HBV monoinfected patients (0.000%, range: 0.000 – 0.284%; p = 0.023). In contrast to HBV-specific T-cell responses, no significant difference regarding frequency and functionality of HIV-specific T-cell responses was observed in HIV/HBV coinfected and HIV monoinfected patients.

Based on these data we propose that HIV infection impairs frequency and functionality of HBV-specific CD4 T-cell responses in HIV/HBV coinfected patients. HIV infection seems to specifically induce monofunctional IL-2-secreting HBV-specific CD4 T cells leading to activation and thereby increased viral replication and turnover of these cells. In further experiments regulatory T cells and exhaustion of HBV-specific T cells will be analyzed to characterize the detailed mechanisms how HIV impairs HBV-specific T-cell responses.