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标题:
慢性乙型肝炎的新型免疫细胞疗法
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作者:
StephenW
时间:
2013-5-28 22:28
标题:
慢性乙型肝炎的新型免疫细胞疗法
慢性乙型肝炎的新型免疫细胞疗法更新时间:2013-5-28 作者:佚名 文章来源:
国际肝病网
强有效的T细胞应答是清除HBV所不可或缺的,但这也恰好是慢性乙型肝炎患者所欠缺的。德国慕尼黑工业大学病毒研究所Krebs等尝试将T细胞导向于病毒感染细胞以清除病毒,并在动物实验中取得了初步成功。
Krebs的方法是在体外通过逆转录载体使CD8+T细胞表达能与HBV包膜蛋白结合的嵌合抗原受体(S-CAR),随后将表达S-CAR的CD8+T细胞被动转入HBV转基因小鼠体内。结果显示,表达S-CAR的CD8+T细胞能识别多种HBV亚型,能被成功植入免疫健全的HBV转基因小鼠,并在小鼠体内扩增。这些T细胞主要定位于肝脏,并在肝内发挥功能,能迅速有效地控制HBV复制,仅引起一过性肝损伤。
该研究提示,循环中的大量病毒抗原并不削弱或过度活化这些植入的表达S-CAR的CD8+T细胞。这种免疫细胞疗法不受人白细胞抗原限制,可加以开发用于人类。
作者:
StephenW
时间:
2013-5-28 22:29
Gastroenterology.
2013 Apr 29. pii: S0016-5085(13)00684-7. doi: 10.1053/j.gastro.2013.04.047. [Epub ahead of print]
T Cells Expressing a Chimeric Antigen Receptor That Binds Hepatitis B Virus Envelop Proteins Control Virus Replication in Mice.
Krebs K
,
Böttinger N
,
Huang LR
,
Chmielewski M
,
Arzberger S
,
Gasteiger G
,
Jäger C
,
Schmitt E
,
Bohne F
,
Aichler M
,
Uckert W
,
Abken H
,
Heikenwalder M
,
Knolle P
,
Protzer U
.
SourceInstitute of Virology, Technische Universität München / Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.
AbstractBACKGROUND & AIMS: Antiviral agents suppress hepatitis B virus (HBV) replication but do not clear the infection. A strong effector T-cell response is required to eradicate HBV, but this does not occur in patients with chronic infection. T cells might be directed toward virus-infected cells by expressing HBV-specific receptors, and thereby clear HBV and help to prevent development of liver cancer. In mice, we studied whether redirected T cells can engraft following adoptive transfer, without prior T-cell depletion, and whether the large amounts of circulating viral antigens inactivate the transferred T cells or lead to uncontrolled, immune-mediated damage.
METHODS: CD8+ T cells were isolated from mice and stimulated using an optimized protocol. Chimeric antigen receptors (CARs) that bind HBV envelope proteins (S-CAR) and activate T cells were expressed on the surface of cells using retroviral vectors. S-CAR-expressing CD8+ T cells, which carried the marker CD45.1, were injected into CD45.2+ HBV transgenic mice. We compared these mice with mice that received CD8+ T cells induced by vaccination, cells that express a CAR without a proper signaling domain, or cells that express a CAR that does not bind HBV proteins (controls).
RESULTS: CD8+ T cells that expressed HBV-specific CARs recognized different HBV subtypes and were able to engraft and expand in immune-competent HBV transgenic mice. Following adoptive transfer, the S-CAR-expressing T cells localized to and functioned in the liver; they rapidly and efficiently controlled HBV replication, compared with controls, causing only transient liver damage. The large amount of circulating viral antigen did not impair or over-activate the S-CAR grafted T cells.
CONCLUSION: T cells with a CAR specific for HBV envelop proteins localize to the livers of mice to reduce HBV replication, causing only transient liver damage. This immune-cell therapy might be developed for patients with chronic hepatitis B, regardless of their HLA-type.
Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
作者:
卡奥卡
时间:
2013-5-28 22:55
“这些T细胞主要定位于肝脏,并在肝内发挥功能,能迅速有效地控制HBV复制”。这种疗法和核苷的作用一样吗?只能控制复制,不能完全杀灭CCCDNA?
作者:
sddp1
时间:
2013-5-29 08:19
本帖最后由 sddp1 于 2013-5-29 08:27 编辑
回复
卡奥卡
的帖子
疗效还有待观察吧,不过从提高或激活自己免疫的方面来控制hbv的感染,比仅仅依靠核苷又多了种方法。让人想起了多年前的自体lak细胞回输治疗CHB
作者:
StephenW
时间:
2013-5-29 20:05
回复
卡奥卡
的帖子
我不完全了解 T细胞免疫.
一般来说, CD8 + T细胞控制病毒:
1。通过杀死被感染的细胞(因此清除细胞内cccDNA)
2。不杀死感染的细胞,但控制/清除
细胞内cccDNA(怎么样,我不知道)
如sddp1说, 它是细胞回输治疗, 成为治疗要走很长的路.
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