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肝胆相照论坛 论坛 学术讨论& HBV English 乙肝表面抗原脉冲树状细胞的免疫原性与安全性 ...
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乙肝表面抗原脉冲树状细胞的免疫原性与安全性 [复制链接]

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发表于 2012-4-13 23:25 |只看该作者 |倒序浏览 |打印
The immune modulator capacity of antigen-pulsed dendritic cells (DC) has been documented in patients with cancers and in animal models of chronic viral infections. Cancer antigen-pulsed DC are now used for treating patients with cancer. But viral antigen-pulsed DC are not used in chronic viral-infected patients because safety of antigen-pulsed DC has not been evaluated in these patients. DC were isolated from human peripheral blood mononuclear cells by culturing with human-grade granulocyte-macrophage colony stimulating factor and interleukin-4. Human blood DC were cultured with hepatitis B surface antigen (HBsAg) for 8 h to prepare HBsAg-pulsed DC. After immunogenicity assessment of HBsAg-pulsed DC in vitro, five million HBsAg-pulsed DC were administered intradermally to five patients with chronic hepatitis B (CHB) 1–3 times. HBsAg-pulsed DC were immunogenic in nature because they produced significantly higher levels of interleukin-12 and interferon- compared to unpulsed DC (P < 0.05). Also, HBsAg-pulsed DC induced proliferation of HBsAg-specific T lymphocytes in vitro. CHB patients injected with HBsAg-pulsed DC did not exhibit generalized inflammation, exacerbation of liver damage, abnormal kidney function, or features of autoimmunity. Administration of HBsAg-pulsed DC induced anti-HBs in two patients and HBsAg-specific cellular immunity in 1 patient. This is the first study about preparation of antigen-pulsed DC using human consumable materials for treating patients with CHB. Because HBsAg-pulsed DC were safe for all patients with CHB and had immune modulation capacity in some patients, phase I and phase II clinical trials with antigen-pulsed DC in CHB and other chronic infections are warranted.

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发表于 2012-4-13 23:26 |只看该作者
抗原刺激的树突状细胞的免疫调节功能在肿瘤患者和慢性病毒感染的动物模型中已有报道。癌细胞抗原刺激的树突状细胞目前并不能应用于治疗肿瘤患者,但是病毒抗原刺激的树突状细胞也不能应用于病毒感染的患者因为抗原刺激的树突状细胞的安全性并没有在这些患者中进行评价。树突状细胞是从人外周血单核细胞中提取出来,并通过人粒-巨噬细胞集落刺激因子以及IL-4共培养获得。人类血树突状细胞与乙肝表面抗原共同培养8小时来制备表面抗原刺激的树突状细胞。经过体外对表面抗原刺激的树突状细胞进行免疫原性碱性鉴定,对5例慢性乙肝患者分1-3次对500万树突状细胞进行皮内注射。表面抗原刺激的树突状细胞存在天然的免疫原性,因为它们产生的IL-12水平和干扰素-γ的水平角未受刺激过的细胞明显升高(P<0.05)。同时表面抗原刺激的树突状细胞在体内能刺激表面抗原特异性T淋巴细胞增殖。慢性乙肝患者经注射表面抗原刺激的树突状细胞后并没有出现全身炎性反应,肝损伤加重,肾功能异常以及自身免疫的特征。其中,两例患者出现表面抗体,1例患者出现表面抗原特异性的细胞免疫。

  这是首次利用人类细胞来制备抗原刺激的树突状细胞并且将其用于慢性乙肝患者治疗的报道。因为对于所有慢性乙肝患者而言,表面抗原刺激的树突状细胞是安全的,同时在部分患者有免疫调节的作用,I期和II期临床试验显示抗原刺激的树突状细胞在慢性乙肝患者和其他慢性感染的患者中是有效的。
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