Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B
Lamivudine treatment can restore T cell responsiveness in chronic hepatitis B
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DOI：
10.1172/jci3731
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发表时间：
1998-09-01
影响因子：
15.9
通讯作者：
Ferrari, C
中科院分区：
文献类型：
--
作者：
Boni, C;Bertoletti, A;Ferrari, C
高病毒和/或抗原载量可能是慢性HBV感染患者中经常观察到的T细胞对B型肝炎病毒（HBV）抗原低反应性的重要原因。拉米夫定治疗降低病毒和抗原载量是研究这一假设的理想模型。对12例B e抗原阳性慢性活动性B型肝炎患者在拉米夫定治疗前和治疗期间进行了HLA Ⅱ类限制性T细胞反应和血清HBV-DNA、HBsAg和HBeAg水平的研究，以评估病毒和/或抗原载量与T细胞反应活力之间可能的相关性。评估细胞对HBV核衣壳抗原和肽的增殖以及循环HBV核衣壳特异性T细胞的频率，以表征CD 4介导的应答。在拉米夫定治疗开始后7-14天，在大多数患者中已经检测到CD 4介导的对HBV核衣壳抗原的应答的高度显著增强。10例患者的这种效应显著且持续，但2例未检测到。它与病毒血症的迅速和显著减少同时发生。有趣的是，拉米夫定还增强了对有丝分裂原和回忆抗原的反应，表明其作用不仅限于HBV特异性T细胞。总之，拉米夫定治疗慢性B型肝炎患者可恢复有效的抗病毒T细胞应答，同时减少病毒血症，表明病毒载量在这些患者T细胞低反应性发病机制中的重要性。由于拉米夫定治疗可以克服T细胞低反应性，联合拉米夫定治疗直接刺激T细胞反应可能是一种有效的策略，以诱导根除慢性HBV感染。
High viral and/or antigen load may be an important cause of the T cell hyporesponsiveness to hepatitis B virus (HBV) antigens that is often observed in patients with chronic HBV infection. Reduction of viral and antigen load by lamivudine treatment represents an ideal model for investigating this hypothesis. HLA class II restricted T cell responses and serum levels of HBV-DNA, HBsAg, and HBeAg were studied before and during lamivudine treatment in 12 patients with hepatitis B e antigen positive chronic active hepatitis B to assess possible correlations between viral and/or antigen load and vigor of the T cell response. Cell proliferation to HBV nucleocapsid antigens and peptides and frequency of circulating HBV nucleocapsid-specific T cells were assessed to characterize CD4-mediated responses. A highly significant enhancement of the CD4-mediated response to HBV nucleocapsid antigens was already detectable in most patients 7-14 d after the start of lamivudine treatment. This effect was dramatic and persistent in 10 patients but undetectable in 2, It occurred concomitant with a rapid and marked reduction of viremia, Interestingly, lamivudine also enhanced the responses to mitogens and recall antigens, showing that its effect was not limited to HBV-specific T cells. In conclusion, an efficient antiviral T cell response can be restored by lamivudine treatment in patients with chronic hepatitis B concurrently with reduction of viremia, indicating the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients. Since lamivudine treatment can overcome T cell hyporeactivity, combining lamivudine with treatments directed to stimulate the T cell response may represent an effective strategy to induce eradication of chronic HBV infection.