Interleukin 21 augments the hepatitis B virus-specific CD8+ T-cell response in vitro in patients coinfected with HIV-1

Objectives: Hepatitis B virus (HBV) and HIV-1 share similar transmission routes, therefore, coinfection with both viruses is frequently observed. In HIV-1-infected patients reduced interleukin 21 (IL-21) serum levels have been reported, which may impair virus-specific CD8(+) T-cell responses. Design: The HBV-specific CD8(+) T cells in patients with and without HIV-1 coinfection were analyzed cross-sectionally and it was tested whether addition of IL-21 in vitro augments HBV-specific CD8(+) T-cell responses. Methods: Patients with persistent HBV monoinfection as well as HIV-1-positive patients with persistent or resolved HBV-infection were studied. The IL-21 serum levels were determined by ELISA and the HBV-specific CD8(+) T-cell response was determined after antigen-specific expansion by intracellular staining of interferon gamma. Results: The HBV-specific CD8(+) T-cell response was significantly higher in HIV-1-negative patients compared with HIV-1-positive patients. Interestingly, within the HIV-1-positive group the magnitude of the response did not differ between patients with chronic or resolved HBV-infection. The IL-21 serum levels were significantly lower in the HIV-1-positive group. Importantly, addition of IL-21 in vitro significantly increased the HBV-specific CD8(+) T-cell response in HIV-1-positive patients, whereas there was no beneficial effect of IL-21 on cells from HBV-monoinfected patients. Conclusion: HIV-1 coinfection is associated with a decreased HBV-specific CD8 T-cell response that can be partially rescued in vitro by addition of IL-21. (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins