Reconstitution of anti‐HIV effector functions of primary human CD8 T lymphocytes by transfer of HIV‐specific αβ TCR genes
Reconstitution of anti‐HIV effector functions of primary human CD8 T lymphocytes by transfer of HIV‐specific αβ TCR genes
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DOI：
10.1002/eji.200425568
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发表时间：
2004-12
影响因子：
5.4
通讯作者：
T. Ueno;M. Fujiwara;H. Tomiyama;M. Onodera;M. Takiguchi
中科院分区：
文献类型：
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作者：
T. Ueno;M. Fujiwara;H. Tomiyama;M. Onodera;M. Takiguchi
我们通过逆转录病毒介导的编码 HIV-1 Pol 蛋白特异性 αβ TCR 的基因转导，重新定向了原代人 CD8 T 细胞的抗原特异性。 TCR 转导的 CD8 T 细胞的大量多克隆群体对用肽脉冲或感染 HIV-1 的靶细胞表现出大量的细胞毒性和细胞因子产生活性，并且它们的功能活性与亲本 CTL 克隆的功能相当。 TCR 转导细胞中也保留了亲本 CTL 克隆的 HLA I 类超型的肽精细特异性和混杂识别。这些细胞中没有同种异体反应的迹象，尽管怀疑这些细胞中已经形成了由转导的 TCR 和内源 TCR 组成的杂合 TCR 二聚体，因为转基因表达对所需 TCR 表面表达的影响有限。此外，TCR 转导细胞在体外表现出对 HIV-1 复制的有效抑制活性，尽管所需 TCR 的表面表达差异导致单个 TCR 转导细胞对肽脉冲靶细胞的功能亲合力存在差异。这些数据表明，通过 HIV 特异性 TCR 的基因转移改造的 HIV 特异性免疫反应性 T 细胞的重建是针对 HIV 感染的免疫治疗应用的潜在替代方案。
We redirected the antigen specificity of primary human CD8 T cells by retrovirus‐mediated transduction of genes encoding αβ TCR specific to HIV‐1 Pol protein. A large polyclonal population of TCR‐transduced CD8 T cells showed substantial cytotoxic and cytokine production activities toward target cells either pulsed with the peptide or infected with HIV‐1, and their functional activities were comparable to those of the parental CTL clone. Peptide fine‐specificity and promiscuous recognition of HLA class I supertypes of the parental CTL clone were also preserved in the TCR‐transduced cells. There were no signs of allogeneic responses in these cells, although hybrid TCR dimers consisting of transduced TCR and endogenous TCR were suspected to have been formed in these cells, as the effect of transgene expression on the surface expression of the desired TCR was limited. Moreover, the TCR‐transduced cells showed potent inhibitory activity against HIV‐1 replication in vitro, although the differential surface expression of the desired TCR resulted in differential functional avidity of individual TCR‐transduced cells toward the peptide‐pulsed target cells. These data suggest that the reconstitution of HIV‐specific immunoreactive T cells engineered by genetic transfer of HIV‐specific TCR is a potential alternative to immunotherapeutic applications against HIV infections.