TRANSFER OF HIV-1-SPECIFIC CYTOTOXIC T-LYMPHOCYTES TO AN AIDS PATIENT LEADS TO SELECTION FOR MUTANT HIV VARIANTS AND SUBSEQUENT DISEASE PROGRESSION

TRANSFER OF HIV-1-SPECIFIC CYTOTOXIC T-LYMPHOCYTES TO AN AIDS PATIENT LEADS TO SELECTION FOR MUTANT HIV VARIANTS AND SUBSEQUENT DISEASE PROGRESSION
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DOI:
10.1038/nm0495-330
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发表时间:
1995-04-01
期刊:
影响因子:
82.9
通讯作者:
LANE, HC
LANE, HC
中科院分区:
医学1区
文献类型:
--
作者:
KOENIG, S;CONLEY, AJ;LANE, HC

文献摘要

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向HIV-1血清阳性志愿者输注针对HIV-1 nef蛋白的扩增的自体细胞毒性T淋巴细胞(CTL)克隆。过继转移该克隆以确定补充CTL活性是否可以降低病毒载量或改善临床病程。出乎意料的是,输注后循环CD 4(-)T细胞下降,病毒载量上升。从患者的血浆或CD 4(-)细胞中获得的一些HIV分离株缺乏nef表位。这些结果表明,病毒变异的主动CTL选择可能有助于艾滋病的发病机制,尽管高水平的循环HIV-1特异性CTL,但仍可能发生临床进展。
An HIV-1-seropositive volunteer was infused with an expanded autologous cytotoxic T lymphocyte (CTL) clone directed against the HIV-1 nef protein. This clone was adoptively transferred to determine whether supplementing CTL activity could reduce viral load or improve clinical course. Unexpectedly, infusion was followed by a decline in circulating CD4(-) T cells and a rise in viral load. Some of the HIV isolates obtained from the plasma or CD4(-) cells of the patient were lacking the nef epitope. These results suggest that active CTL selection of viral variants could contribute to the pathogenesis of AIDS and that clinical progression can occur despite high levels of circulating HIV-1-specific CTLs.