The functional CD8 T cell response to HIV becomes type-specific in progressive disease.
The functional CD8 T cell response to HIV becomes type-specific in progressive disease.
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在进行性疾病中，功能性 CD8 T 细胞对 HIV 的反应变得具有类型特异性。
DOI：
10.1172/jci16028
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
Shankar,Premlata
中科院分区：
文献类型：
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作者：
Lee,SangKyung;Xu,Zhan;Lieberman,Judy;Shankar,Premlata
通过实验室检测对一致表位的反应，可以在整个HIV疾病中发现高水平的HIV特异性CD8 T细胞。在急性感染中，抗病毒CD8 T细胞反应的动态与病毒血症的下降密切相关。然而，在慢性感染中，尽管检测到针对更广泛表位的反应，但病毒特异性CD8T细胞显然无法控制病毒复制。为了研究CD8T细胞对一致表位的反应是否由于免疫压力驱动的病毒进化而在慢性期失去了体内相关性，我们将CD8T细胞反应与感染实验室适应的HIVIIIB或患者自身病毒的CD4T细胞靶标进行了比较。干扰素-γ应答的幅度随着疾病的进展而下降，尤其是对自体病毒的反应。通过对T细胞受体β链可变(TCRBV)基因的测序，确定HIVIIIB和自体病毒应答细胞的T细胞受体克隆型。在3名无症状供者中，2名患者的主要克隆型重叠，而在5名有症状的患者中，对HIVIIIBV有反应的TCR克隆型与对自体病毒有反应的TCR克隆型完全不同。此外，在细胞溶解试验中，来自对实验室适应病毒或自体病毒反应的干扰素-γ+细胞的T细胞株在具有相同TCR克隆型的无症状受试者中交叉识别感染这两种病毒的靶细胞，而在具有不同克隆型的进展期受试者中不识别。因此，在晚期患者中，识别共同表位的病毒特异性CD8T细胞从早期的反应中持续存在，但不再有效地识别自体病毒。
High levels of HIV-specific CD8 T cells are demonstrable throughout HIV disease using laboratory assays that measure responses to consensus epitopes. In acute infection, the dynamics of the antiviral CD8 T cell response correlate well with the decline in viremia. However in chronic infection, although responses are detected against a broader spectrum of epitopes, virus-specific CD8 T cells are apparently unable to control viral replication. To investigate whether CD8 T cells responding to consensus epitopes may have lost their in vivo relevance in the chronic phase because of viral evolution driven by immune pressure, we compared the CD8 T cell response to CD4 T cell targets infected with either lab-adapted HIVIIIBor the patient’s own virus. The magnitude of the IFN-γ response declined with disease progression, especially to autologous virus. T cell receptor (TCR) clonotypes of HIVIIIBand autologous virus–responding cells were determined by sequencing TCR β chain variable (TCRBV) genes. In two of three asymptomatic donors, the dominant clonotypes overlapped, whereas in five symptomatic patients, the TCR clonotypes responding to HIVIIIBvirus were completely different from those responding to autologous virus. Moreover, in cytolytic assays, T cell lines derived from IFN-γ+cells responding to lab-adapted or autologous virus cross-recognized target cells infected with either virus in asymptomatic subjects with shared TCR clonotypes but not in progressors with differing clonotypes. Therefore, in advanced-stage patients, viral-specific CD8 T cells recognizing consensus epitopes persist from an earlier response but no longer effectively recognize autologous virus.