Loss of virus-specific CD4+ T cells with increases in viral loads in the chronic phase after vaccine-based partial control of primary simian immunodeficiency virus replication in macaques
Loss of virus-specific CD4+ T cells with increases in viral loads in the chronic phase after vaccine-based partial control of primary simian immunodeficiency virus replication in macaques
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DOI：
10.1099/vir.0.79890-0
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发表时间：
2004-07-01
影响因子：
3.8
通讯作者：
Matano, T
中科院分区：
文献类型：
--
作者：
Lun, WH;Takeda, A;Matano, T
病毒特异性细胞免疫反应在控制免疫缺陷病毒复制中发挥重要作用。然而，诱导病毒特异性细胞免疫反应的疫苗的临床前试验未能抑制猿猴免疫缺陷病毒（SIV）在猕猴中的复制。先前已开发出一种有缺陷的原病毒 DNA 疫苗系统，可有效诱导病毒特异性 CD8(+) T 细胞反应。接种疫苗的猕猴表现出病毒载量减少，但未能抑制 SIVmac239 复制。在这项研究中，对显示出部分控制 SIV 复制的猕猴进行了随访，看看它们在慢性期是否或如何失去这种控制。其中两人在攻击后约 4 或 8 个月表现出病毒载量增加，最终患上艾滋病。通过检测SIV特异性γ干扰素产生对SIV特异性T细胞水平的分析表明，这两只猕猴即使在失去控制后仍保留了SIV特异性CD8+T细胞，但当血浆病毒载量增加时失去了SIV特异性CD4+T细胞。剩下的猕猴将病毒载量保持在较低水平，并维持 SIV 特异性 CD4(+) T 细胞和 CD8(+) T 细胞超过 3 年。使用接种了表达 Gag 的仙台病毒载体的猕猴进行的其他分析也发现，病毒血症控制丧失，在 SIV 感染的慢性阶段，SIV 特异性 CD4+ T 细胞丧失。因此，能够响应SIV抗原产生IFN-γ的SIV特异性CD4(+) T细胞通过基于疫苗的原代SIV复制的部分控制得以保留，但随着慢性期控制的取消而丢失。
Virus-specific cellular immune responses play an important role in the control of immunodeficiency virus replication. However, preclinical trials of vaccines that induce virus-specific cellular immune responses have failed to contain simian immunodeficiency virus (SIV) replication in macaques. A defective provirus DNA vaccine system that efficiently induces virus-specific CD8(+) T-cell responses has previously been developed. The vaccinated macaques showed reduced viral loads, but failed to contain SIVmac239 replication. In this study, macaques that showed partial control of SIV replication were followed up to see if or how they lost this control in the chronic phase. Two of them showed increased viral loads about 4 or 8 months after challenge and finally developed AIDS. Analysis of SIV-specific T-cell levels by detection of SIV-specific gamma interferon production revealed that these two macaques maintained SIV-specific CD8(+) T cells, even after loss of control, but lost SIV-specific CD4(+) T cells when plasma viral loads increased. The remaining macaque kept viral loads at low levels and maintained SIV-specific CD4(+) T cells, as well as CD8(+) T cells, for more than 3 years. Additional analysis using macaques vaccinated with a Gag-expressing Sendai virus vector also found loss of viraemia control, with loss of SIV-specific CD4+ T cells in the chronic phase of SIV infection. Thus, SIV-specific CD4(+) T cells that were able to produce IFN-gamma in response to SIV antigens were preserved by the vaccine-based partial control of primary SIV replication, but were lost with abrogation of control in the chronic phase.