INFECTION AND APOPTOTIC CELL-DEATH OF CD4+ T-CELLS DURING AN IMMUNE-RESPONSE TO HIV-1-PULSED DENDRITIC CELLS

INFECTION AND APOPTOTIC CELL-DEATH OF CD4+ T-CELLS DURING AN IMMUNE-RESPONSE TO HIV-1-PULSED DENDRITIC CELLS
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DOI:
10.1089/aid.1994.10.61
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发表时间:
1994-01-01
影响因子:
1.5
通讯作者:
STEINMAN, RM
STEINMAN, RM
中科院分区:
医学4区
文献类型:
--
作者:
CAMERON, PU;POPE, M;STEINMAN, RM

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相互作用的树突状细胞和辅助性CD 4(+)淋巴细胞形成了一个允许HIV-1复制的微环境。这种病毒只需要在开始时被脉冲到树突细胞上,然后树突细胞将HIV-1转移到对呈递抗原或超抗原有反应的淋巴细胞上。我们已经在这个系统中探索了潜在的机制,因为它提供了抗原反应性的原代T细胞感染的模型。用HIV-1刺激T细胞比刺激树突细胞导致更少的后续感染。后一种脉冲在AZT存在下有效地发生。对相互作用的树突状细胞和T细胞的直接检查揭示了许多淋巴细胞(包括合胞体)广泛产生p24。大多数应答T细胞在共培养期间死亡。细胞凋亡占这种死亡的大部分,如DNA内切核酸原位缺口翻译分析和DNA结合染料染色的亚二倍体概况所揭示的。因此,抗原递呈树突状细胞和T细胞之间产生的微环境揭示了HIV-1的细胞病变潜力,因为抗原反应性T细胞的凋亡会导致广泛而快速的死亡。
Interacting dendritic cells and helper CD4(+) lymphocytes form a microenvironment that is permissive for HIV-1 replication. The virus need only be pulsed initially onto the dendritic cells, which then transfer HIV-1 to the lymphocytes that are responding to presented antigens or superantigens. We have pursued underlying mechanisms in this system, because it provides a model for the infection of antigen-reactive, primary T cells. Pulsing the T cells with HIV-1 results in much less of a subsequent infection than does pulsing the dendritic cells. The latter pulse occurs effectively in the presence of AZT. Direct examination of the interacting dendritic cells and T cells reveals extensive production of p24 by many of the lymphocytes, including syncytia. The majority of the responding T cells die during the coculture. Apoptosis accounts for much of this death as revealed by in situ nick translation assays for DNA endonucleolysis, and hypodiploid profiles on staining with DNA-binding dyes. Therefore the microenviromnent that is generated between antigen-presenting dendritic cells and T cells reveals the cytopathic potential of HIV-1, because there is such extensive and rapid death by apoptosis of antigen-reactive T cells.