Lau George K K, Suri Deepak, Liang Raymond, Rigopoulou Eirini I, Thomas Mark G, Mullerova Ivana, Nanji Amin, Yuen Siu-Tsan, Williams Roger, Naoumov Nikolai V
Institute of Hepatology, University College London, London, England.
Gastroenterology. 2002 Mar;122(3):614-24. doi: 10.1053/gast.2002.31887.
BACKGROUND & AIMS: Impaired T-cell reactivity is believed to be the dominant cause of chronic hepatitis B virus (HBV) infection. We characterized HBV-specific T-cell responses in chronic hepatitis B surface antigen carriers who received bone marrow from HLA-identical donors with natural immunity to HBV and seroconverted to antibody to hepatitis B surface antigen.
T-cell reactivity to HBV antigens and peptides was assessed in a proliferation assay, the frequency of HBV core- and surface-specific T cells was quantified directly by ELISPOT assays, and T-cell subsets were analyzed by flow cytometry.
CD4+ T-cell reactivity to HBV core was common in bone marrow donors and the corresponding recipients after hepatitis B surface antigen clearance, whereas none reacted to surface, pre-S1, or pre-S2 antigens. Furthermore, CD4+ T cells from donor/recipient pairs recognized similar epitopes on hepatitis B core antigen; using polymerase chain reaction for the Y chromosome, the recipients' CD4+ T lymphocytes were confirmed to be of donor origin. The frequency of core-specific CD4+ and CD8+ T cells was several-fold higher than those specific for surface antigen.
This study provides the first evidence in humans that transfer of hepatitis B core antigen-reactive T cells is associated with resolution of chronic HBV infection. Therapeutic immunization with HBV core gene or protein deserves further investigation in patients with chronic hepatitis B.
T细胞反应性受损被认为是慢性乙型肝炎病毒（HBV）感染的主要原因。我们对慢性乙型肝炎表面抗原携带者的HBV特异性T细胞反应进行了特征分析，这些携带者接受了来自对HBV具有天然免疫力的HLA相同供体的骨髓，并血清转化为乙型肝炎表面抗原抗体。
通过增殖试验评估T细胞对HBV抗原和肽的反应性，通过ELISPOT试验直接定量HBV核心和表面特异性T细胞的频率，并通过流式细胞术分析T细胞亚群。
在骨髓供体和乙型肝炎表面抗原清除后的相应受者中，CD4+T细胞对HBV核心的反应性很常见，而对表面、前S1或前S2抗原均无反应。此外，供体/受体对的CD4+T细胞识别乙型肝炎核心抗原上的相似表位；使用Y染色体聚合酶链反应，证实受者的CD4+T淋巴细胞来源于供体。核心特异性CD4+和CD8+T细胞的频率比表面抗原特异性T细胞高几倍。
本研究首次在人类中提供证据表明，乙型肝炎核心抗原反应性T细胞的转移与慢性HBV感染的消退有关。用HBV核心基因或蛋白进行治疗性免疫值得在慢性乙型肝炎患者中进一步研究。
