The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer-cell subsets associated with high levels of HIV-1 viremia
The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer-cell subsets associated with high levels of HIV-1 viremia
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DOI：
10.1182/blood-2009-06-226332
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发表时间：
2009-10-29
期刊：
影响因子：
20.3
通讯作者：
Mavilio, Domenico
中科院分区：
文献类型：
--
作者：
Brunetta, Enrico;Fogli, Manuela;Mavilio, Domenico
HIV-1 已开发出多种策略来逃避自然杀伤 (NK) 细胞的抗病毒功能。这些机制之一是 HIV-1 诱导高度功能失调的 NK 细胞亚群的扩张。在这里，我们对一大群处于感染早期或慢性阶段的 HIV-1 感染患者进行横向和纵向分析。我们证明，唾液酸结合免疫球蛋白样凝集素 7 (Siglec-7) 表面表达的显着下降代表了异常 NK 细胞失调的最早标志，这种失调先于 CD56 下调，主要发生在慢性 HIV-1 病毒血症患者中。 Siglec-7 和 CD56 的联合检测可以识别 2 个新的病理性 NK 细胞亚群，这些亚群优先在 HIV-1 感染的早期 (Siglec-7(-)/CD56(+)) 或慢性 (Siglec-7(-)/CD56(+)) 阶段扩增。值得注意的是，这些表型异常与 NK 细胞功能的进行性和明显损伤直接相关。上述 NK 细胞异常仅在存在高水平病毒复制的情况下才能观察到，而在 HIV-1 病毒血症较低或无法检测到的患者中观察不到，例如长期无进展者或接受抗逆转录病毒治疗的患者。 Siglec-7(-)/CD56(+)和Siglec-7(-)/CD56(+)病理性NK细胞的高频率反映了HIV-1感染的免疫和临床状态，也可以跟踪治疗的有效性。 （血。2009；114：3822-3830）
HIV-1 has developed several strategies to evade natural killer (NK)-cell antiviral functions. One of these mechanisms is the HIV-1-induced expansion of highly dysfunctional NK-cell subsets. Here, we analyze a large cohort of HIV-1-infected patients in early or chronic phases of infection, both cross-sectionally and longitudinally. We demonstrate that a striking decrease in the surface expression of sialic acid-binding immunoglobulin-like lectin 7 (Siglec-7) represents the earliest marker of the aberrant NK-cell dysregulation, which precedes the down-modulation of CD56 mostly occurring in patients with chronic HIV-1 viremia. The combined detection of Siglec-7 and CD56 allows the identification of 2 new pathologic NK-cell subsets expanded preferentially in early (Siglec-7(-)/CD56(+)) or chronic (Siglec-7(-)/CD56(+)) stages of HIV-1 infection. Remarkably, these phenotypic abnormalities were directly associated with progressive and distinct impairments of NK-cell functions. The aforementioned NK-cell aberrancies could be observed only in the presence of high levels of viral replication and not in patients with low or undetectable HIV-1 viremia, such as long-term nonprogressors or patients having undergone anti-retroviral therapy. High frequencies of Siglec-7(-)/CD56(+) and Siglec-7(-)/CD56(+) pathologic NK cells reflect the immune and clinical status of HIV-1 infection and can also track the effectiveness of therapy. (Blood. 2009; 114: 3822-3830)