Preferential survival of CD4+ T lymphocytes engineered with anti-human immunodeficiency virus (HIV) genes in HIV-infected individuals
Preferential survival of CD4+ T lymphocytes engineered with anti-human immunodeficiency virus (HIV) genes in HIV-infected individuals
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DOI：
10.1089/hum.2005.16.1065
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发表时间：
2005-09-01
影响因子：
4.2
通讯作者：
Lane, HC
中科院分区：
文献类型：
--
作者：
Morgan, RA;Walker, R;Lane, HC
本研究检测了基因工程CD4(+) T淋巴细胞在人类免疫缺陷病毒（HIV）感染者体内的安全性和相对存活率。研究人员招募了10对HIV感染不一致的同卵双胞胎，其中未感染的双胞胎作为淋巴细胞供体。10名受试者接受共19次单独输注逆转录病毒载体转导的CD4+富集T细胞治疗。使用载体特异性PCR检测，在外周血中监测对照（neo基因）或抗hiv基因（反义反式激活反应[TAR]元件和/或反式显性Rev）工程淋巴细胞3年。10例患者中有9例（19例输注中有15例）的数据显示，在输注后的几周内，含有抗hiv基因的CD4（+）淋巴细胞优先存活。在长期研究的6名患者中（100 - 100周），只有含有抗hiv基因的T细胞一直被检测到。此外，在高病毒载量期间治疗的患者中观察到含有抗hiv基因的T细胞的显着生存优势。因此，这些数据有力地支持了抗hiv基因为T细胞提供生存优势和对HIV-1（+）个体潜在益处的假设。
The present study examined the safety and relative in vivo survival of genetically engineered CD4(+) T lymphocytes in human immunodeficiency virus (HIV)-infected individuals. Ten pairs of identical twins discordant for HIV infection were recruited, with the uninfected twin serving as the lymphocyte donor. Ten subjects were treated with a total of 19 separate infusions of retroviral vector-transduced CD4+ enriched T cells. Control (neo gene) or anti-HIV gene (antisense trans-activation response [TAR] element and/or trans-dominant Rev)-engineered lymphocytes were monitored in peripheral blood for 3 years, using a vector-specific PCR assay. Data from 9 of the 10 patients (15 of the 19 infusions) demonstrated preferential survival of CD4(+) lymphocytes containing the anti-HIV gene(s) in the immediate weeks after infusion. In six of six patients studied long term (> 100 weeks), only T cells containing the anti-HIV genes were consistently detected. In addition, a marked survival advantage of anti-HIV gene-containing T cells was observed in a patient treated during a period of high viral load. Thus, these data strongly support the hypothesis that anti-HIV genes afford a survival advantage to T cells and potential benefit to HIV-1(+) individuals.