Evidence for rapid disappearance of initially expanded HIV-specific CD8(+) T cell clones during primary HIV infection
Evidence for rapid disappearance of initially expanded HIV-specific CD8(+) T cell clones during primary HIV infection
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DOI：
10.1073/pnas.94.18.9848
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发表时间：
1997-09-02
影响因子：
11.1
通讯作者：
Fauci, AS
中科院分区：
文献类型：
--
作者：
Pantaleo, G;Soudeyns, H;Fauci, AS
在原发性HIV感染期间，病毒血症初始爆发的下调被认为主要由HIV特异性细胞毒性T淋巴细胞介导，并且这种应答的出现与T细胞受体库的主要扰动相关。在原发性感染患者中分析病毒特异性细胞毒性T淋巴细胞的T细胞受体库的变化，以了解细胞免疫应答控制病毒传播和复制的失败。该分析表明，参与初次免疫应答的大量HIV特异性T细胞克隆迅速消失。这种消失不是这些克隆识别的病毒表位突变的结果。提供的证据表明，高剂量耐受性或克隆衰竭等现象可能参与这些单克隆扩增的HIV特异性细胞毒性T细胞克隆的消失，这些研究结果应该提供深入了解艾滋病毒，并可能其他病毒，逃避宿主的免疫反应在原发感染。
Down-regulation of the initial burst of viremia during primary HIV infection is thought to be mediated predominantly by HIV-specific cytotoxic T lymphocytes, and the appearance of this response is associated with major perturbations of the T cell receptor repertoire. Changes in the T cell receptor repertoire of virus-specific cytotoxic T lymphocytes were analyzed in patients with primary infection to understand the failure of the cellular immune response to control viral spread and replication. This analysis demonstrated that a significant number of HIV-specific T cell clones involved in the primary immune response rapidly disappeared. The disappearance was not the result of mutations in the virus epitopes recognized by these clones. Evidence is provided that phenomena such as high-dose tolerance or clonal exhaustion might be involved in the disappearance of these monoclonally expanded HIV-specific cytotoxic T cell clones, These findings should provide insights into how HIV, and possibly other viruses, elude the host immune response during primary infection.