COMBINED INTRACELLULAR AND EXTRACELLULAR IMMUNIZATION AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION WITH A HUMAN ANTI-GP120 ANTIBODY
COMBINED INTRACELLULAR AND EXTRACELLULAR IMMUNIZATION AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION WITH A HUMAN ANTI-GP120 ANTIBODY
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DOI：
10.1073/pnas.91.13.5932
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发表时间：
1994-06-21
影响因子：
11.1
通讯作者：
MARASCO, WA
中科院分区：
文献类型：
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作者：
CHEN, SY;KHOURI, Y;MARASCO, WA
在这项研究中，人的CD4(+)T淋巴细胞系被转导来分泌一种与人类免疫缺陷病毒1型(HIV-1)包膜蛋白的CD4结合部位发生反应的广泛中和的人源单抗F105的Fab片段。在感染HIV-1的转导细胞中，新生的Fab片段与HIV-1包膜蛋白结合在细胞内，抑制HIV-1的产生。分泌的Fab片段能够中和无细胞的HIV-1。此外，新生的Fab片段可以通过细胞内结合到逃脱细胞外F105抗体中和的包膜突变体来抑制HIV-1的产生。表达的Fab片段的细胞内外结合活性有效地阻止了细胞病变合胞体的形成和感染性病毒的产生。因此，这些产生抗体的T淋巴细胞不仅能抵抗HIV-1感染，还能通过分泌中和抗体来保护周围的淋巴细胞。这种细胞内和细胞外免疫相结合的新策略可能对艾滋病和其他疾病的基因治疗有用。
In this study, a human CD4(+) T lymphocyte line was transduced to secrete Fab fragments of a broadly neutralizing human monoclonal antibody F105 that reacts with the CD4-binding site of human immunodeficiency virus type 1 (HIV-1) envelope protein. In the transduced cells infected with HIV-1, the nascent Fab fragments bind intracellularly to the HIV-1 envelope protein and inhibit HIV-1 production. The secreted Fab fragments are able to neutralize cell-free HIV-1. In addition, the nascent Fab fragments can inhibit HIV-1 production by binding intracellularly to envelope mutants that escape neutralization by extracellular F105 antibody. The combined intra- and extracellular binding activities of the expressed Fab fragments result in the efficient blocking of cytopathic syncytium formation and infectious virus production. Thus, these antibody-producing T lymphocytes are not only resistant to HIV-1 infection but also can protect surrounding lymphocytes by secreting neutralizing antibodies. This novel strategy of combining intracellular and extracellular immunization may be useful for gene therapy of AIDS and other diseases.