Cross-sectional study on hepatitis B virus-specific CD4+ T cell immune response after liver transplantation

Abstract

Background/Aims: Hepatitis B virus (HBV)-specific T cells play a critical role in controlling viralreplication and maintaining the protective immunity against HBV reinfection. In this study, wecharacterized HBV-specific CD4+ T cell-mediated immune response after liver transplantation forHBV-associated liver disease.Methods: The function and frequency of circulating HBV-specific CD4+ T cells were studied byproliferation and enzyme-linked immunospot assays in 40 recipients without evidence of HBVrecurrence at 1 year (n=29) or at 5 years (n=11) after liver transplantation, and in 6 recipients withrecurrent HBV infection.Results: T cell proliferation response to mitogen (phytohemagglutinin) and recall antigen (tetanustoxoid) were maintained in recipients at 1 and 5 years after transplantation, comparable to those ofpre-transplant patients and healthy subjects, however, HBV-specific CD4+ T cell proliferationresponse and frequency significantly declined to either undetectable or very low levels. In recipientswith HBV recurrence, despite immunosuppression, a significant HBV-specific CD4+ T cell responsewas detectable, but did not correlate with viral load, histology and levels of liver transaminases.Conclusions: HBV-specific CD4+ T cell immune responses may evanesce with clearance of viralantigens after liver transplantation, suggesting the necessity of retaining a long-term prophylactictreatment or developing new strategies to induce HBV-specific immunity for prevention of HBVrecurrence.Figure The median levels of T cell proliferation (a) and median frequencies of interferon (IFN)-γ-secreting T cells (b) in response to in vitro challenge with hepatitis B surface (HBsAg) and coreantigen (HBcAg) in 11 HBV-naïve and 23 HBV-immune healthy subjects, 29 HBV-infected patientsbefore liver transplantation (LT), 29 at 1 year post-LT, 11 at 5 years post-LT, as well as 6 recipientswith recurrent HBV infection. * Significantly lower than pre-LT and HBV immune controls, **significantly lower than HBV immune control (P < 0.05, Mann-Whitney U test). Dot lines indicatethe significant level of HBV-specific immune response.