Mechanism of restoration of immune responses of patients with chronic hepatitis B during lamivudine therapy: increased antigen processing and presentation by dendritic cells
Mechanism of restoration of immune responses of patients with chronic hepatitis B during lamivudine therapy: increased antigen processing and presentation by dendritic cells
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DOI：
10.1111/j.1365-2893.2010.01300.x
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发表时间：
2011-03-01
影响因子：
2.5
通讯作者：
Onji, M.
中科院分区：
文献类型：
--
作者：
Akbar, S. M. F.;Horiike, N.;Onji, M.
据报道，慢性B型肝炎（CH B）患者在接受拉米夫定治疗后可恢复宿主免疫力;然而，这种治疗的潜在机制尚未确定。本研究探讨了抗原呈递树突状细胞（DC）在恢复宿主免疫中的作用。从23例CHB患者开始拉米夫定治疗前和治疗后1、3和12个月的外周血中分离循环DC。异基因混合白细胞反应检测DC的非抗原特异性增殖。用B型肝炎表面抗原（HBsAg）刺激树突状细胞，制备HBsAg致敏的DC。检测负载Ag的DC的增殖能力和白细胞介素（IL）-12和干扰素（IFN）-γ的产生。拉米夫定治疗后1个月，循环中未脉冲DC和HBsAg脉冲DC的T细胞增殖能力均显著高于治疗前（P < 0.05）。经拉米夫定治疗后，经Ag-DC脉冲处理的DC产生的IL-12和IFN-γ水平也显著高于治疗前（P < 0.05）。经拉米夫定治疗的CHB患者DC经HBsAg致敏后，以抗原特异性方式诱导CHB患者T细胞增殖（P < 0.05）。然而，与拉米夫定治疗后1个月相比，拉米夫定治疗后3个月和12个月DC的T细胞刺激能力没有显著增加。作为拉米夫定治疗结果的免疫恢复至少部分地通过DC的活化来调节。然而，随着治疗持续时间的进展，未观察到DC的进行性活化，表明这种病毒清除机制的局限性。
Restoration of host immunity has been reported in patients with chronic hepatitis B (CHB) after treatment with lamivudine; however, the underlying mechanisms of this treatment have not been determined. This study examined the role of antigen-presenting dendritic cells (DC) in restoration of host immunity. Circulating DC were isolated from peripheral blood of 23 patients with CHB before and 1, 3, and 12 months after starting lamivudine therapy. The non-antigen-specific proliferation of DC was assessed in allogenic mixed leucocyte reaction. Dendritic cells were cultured with hepatitis B surface antigen (HBsAg) to prepare HBsAg-pulsed DC. Proliferative capacity and production of interleukin (IL)-12 and interferon (IFN)-gamma of HBsAg-pulsed DC were evaluated. Circulating unpulsed DC and HBsAg-pulsed DC showed significantly higher levels of T-cell proliferation capacities 1 month after lamivudine therapy compared to proliferation levels before therapy (P < 0.05). HBsAg-pulsed DC also produced significantly higher levels of IL-12 and IFN-gamma with lamivudine therapy compared to levels before therapy (P < 0.05). HBsAg-pulsed DC from lamivudine-treated patients induced proliferation of T cells of patients with CHB in an antigen-specific manner (P < 0.05). However, T-cell stimulatory capacity of DC did not increase significantly 3 and 12 months after lamivudine therapy compared to 1 month after lamivudine therapy. Immune restoration as a result of lamivudine therapy is regulated at least in part by activation of DC. However, progressive activation of DC was not seen as treatment duration progressed, indicating the limitations of this mechanism of viral clearance.