Interleukin-2 Production by Polyfunctional HIV-1-Specific CD8T Cells Is Associated With Enhanced Viral Suppression
Interleukin-2 Production by Polyfunctional HIV-1-Specific CD8T Cells Is Associated With Enhanced Viral Suppression
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DOI：
10.1097/qai.0b013e318224d2e9
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发表时间：
2011-10-01
影响因子：
3.6
通讯作者：
Goepfert, Paul A.
中科院分区：
文献类型：
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作者：
Akinsiku, Olusimidele T.;Bansal, Anju;Goepfert, Paul A.
背景：测量HIV-1特异性CD8 T细胞反应诱导的方法通常依赖于间接效应功能的测量，如趋化因子和细胞因子的产生，这可能不能反映入侵病原体的直接消除。对CD8T细胞抑制HIV-1复制的功能能力的评估已被视为有效免疫反应的替代标志。为了进一步研究这一点，我们在体外抑制试验中检测了病毒特异性CD8 T细胞抑制HIV-1复制的能力。方法：我们从没有接受抗逆转录病毒治疗的慢性HIV感染者(n=5)和对照组(n=4)的外周血单个核细胞中扩增了15个表位特异性CD8 T细胞系。检测细胞株产生效应分子(CD107a、IL-2、干扰素-γ、肿瘤坏死因子-α、穿孔素)和抑制自体CD8T细胞病毒复制的能力。结果：细胞内细胞因子染色显示，进展期和控制期的CD8T细胞株具有相似的效应功能。相反，我们观察到，与进展期相比，来自控制者的CD8T细胞株显示出更强的病毒抑制能力。病毒抑制是以主要组织相容性复合体依赖的方式介导的，并被发现与多功能IL-2(+)CD8 T细胞反应相关。结论：利用一种灵敏的体外抑制试验，我们证明CD8 T细胞介导的抑制HIV-1复制是HIV-1控制的标志。抑制能力与多功能IL-2的产生相关。评估CD8T细胞介导的抑制可能是评估疫苗诱导应答的重要工具。
Background: Assays to measure the induction of HIV-1-specific CD8 T-cell responses often rely on measurements of indirect effector function such as chemokine and cytokine production, which may not reflect direct elimination of an invading pathogen. Assessment of the functional ability of CD8 T cells to suppress HIV-1 replication has been viewed as a surrogate marker of an effectual immune response. To further investigate this, we measured the capacity of virus-specific CD8 T cells to inhibit HIV-1 replication in an in vitro suppression assay.Methods: We expanded 15 epitope-specific CD8 T-cell lines from peripheral blood mononuclear cells of chronically HIV-infected progressors (n = 5) and controllers (n = 4) who were not on antiretroviral therapy. Cell lines were tested for their ability to produce effector molecules (CD107a, IL-2, IFN-gamma, TNF-alpha, perforin) and suppress virus replication in autologous CD4 T cells.Results: CD8 T-cell lines from both progressors and controllers had largely similar effector function profiles as determined by intracellular cytokine staining. In contrast, we observed that CD8 T-cell lines derived from controllers show enhanced virus suppression when compared with progressors. Virus suppression was mediated in an major histocompatibility complex-dependent manner and found to correlate with a polyfunctional IL-2(+) CD8 T-cell response.Conclusions: Using a sensitive in vitro suppression assay, we demonstrate that CD8 T-cell-mediated suppression of HIV-1 replication is a marker of HIV-1 control. Suppressive capacity was found to correlate with polyfunctional IL-2 production. Assessment of CD8 T-cell-mediated suppression may be an important tool to evaluate vaccine-induced responses.