Direct, help-independent priming of CD8+ T cells by adeno-associated virus-transduced hepatocytes.

Direct, help-independent priming of CD8+ T cells by adeno-associated virus-transduced hepatocytes.
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DOI:
10.1002/hep.23745
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发表时间:
2010-09
期刊:
影响因子:
13.5
通讯作者:
Crispe, Ian N.
Crispe, Ian N.
中科院分区:
医学1区
文献类型:
--
作者:
Wuensch, Sherry A.;Spahn, Jessica;Crispe, Ian N.

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HBV和HCV经常建立慢性感染,提出了T细胞在肝脏中是否启动不良的问题。为了确定不同细胞类型在CD 8 + T细胞活化中对肝细胞抗原的作用,我们使用腺相关病毒将卵清蛋白递送至肝细胞。与CD 8 + T细胞相反,CD 4 + T细胞未被活化。即使在不存在内源性CD 4 + T细胞的情况下,CD 8 + T细胞也被活化;然而,在肝脏中,这些细胞在PD-1中高而在CD 127中低。嵌合体实验表明,这些CD 8 + T细胞在实体组织细胞上被激活。在没有CD 4 + T细胞帮助的情况下,直接在非造血细胞上引发CD 8 + T细胞导致次优的T细胞活化。这可以解释慢性肝脏感染中CD 8 + T细胞功能受损的原因。
Both HBV and HCV frequently establish chronic infection, raising the question whether T cells are poorly primed in the liver. To determine the role of different cell types in the activation of CD8+ T cells against hepatocellular antigens, we used an Adeno-Associated Virus to deliver ovalbumin to hepatocytes. In contrast to CD8+ T cells, CD4+ T cells were not activated. The CD8+ T cells were activated even in the absence of endogenous CD4+ T cells; however in the liver these cells were high in PD-1 and low in CD127. Chimera experiments revealed that these CD8+ T cells were activated on a solid tissue cell. Priming of CD8+ T cells directly on non-hematopoietic cells, in the absence of CD4+ T cell help, results in suboptimal T cell activation. This could explain the impaired function of CD8+ T cells seen in chronic liver infection.
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