Functional reconstitution of class II MHC-Restricted T cell immunity mediated by retroviral transfer of the αβ TCR complex
Functional reconstitution of class II MHC-Restricted T cell immunity mediated by retroviral transfer of the αβ TCR complex
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DOI：
10.4049/jimmunol.165.1.528
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发表时间：
2000-07-01
影响因子：
4.4
通讯作者：
Kitamura, T
中科院分区：
文献类型：
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作者：
Fujio, K;Misaki, Y;Kitamura, T
将α β TCR基因转移到T淋巴细胞中将提供通过增加肿瘤或病原体特异性T淋巴细胞的频率来增强Ag特异性免疫的手段。我们产生了一个有效的α β TCR基因转移系统，使用两个独立的单顺反子逆转录病毒载体携带的II类MHC限制性α或β TCR基因特异性鸡卵清蛋白。该系统使我们能够在44%的CD 4（+）T细胞中表达克隆型TCR。在体外培养体系中，转导细胞对OVA（323 - 339）肽有明显的免疫应答，其对抗原的免疫应答与转基因小鼠T淋巴细胞的免疫应答相当，连续转移小鼠体内可诱导抗原特异性迟发型超敏反应。这些结果表明，α β TCR基因转移到外周血T淋巴细胞可以重建Ag特异性免疫。我们在这里提出，这种方法提供了一个新的方法来操纵免疫反应和免疫治疗的基础。
Transfer of the alpha beta TCR genes into T lymphocytes will provide a means to enhance Ag-specific immunity by increasing the frequency of tumor- or pathogen-specific T lymphocytes. We generated an efficient alpha beta TCR gene transfer system using two independent monocistronic retrovirus vectors harboring either of the class II MHC-restricted alpha or beta TCR genes specific for chicken OVA. The system enabled us to express the clonotypic TCR in 44% of the CD4(+) T cells. The transduced cells showed a remarkable response to OVA(323-339) peptide in the in vitro culture system, and the response to the Ag was comparable with those of the T lymphocytes derived from transgenic mice harboring OVA-specific TCR, Adoptive transfer of the TCR-transduced cells in mice induced the Ag-specific delayed-type hypersensitivity in response to OVA(323-339) challenge. These results indicate that alpha beta TCR gene transfer into peripheral T lymphocytes can reconstitute Ag-specific immunity. We here propose that this method provides a basis for a new approach to manipulation of immune reactions and immunotherapy.