Dynamics and Consequences of IL-21 Production in HIV-Infected Individuals: A Longitudinal and Cross-Sectional Study
Dynamics and Consequences of IL-21 Production in HIV-Infected Individuals: A Longitudinal and Cross-Sectional Study
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DOI：
10.4049/jimmunol.0901967
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发表时间：
2010-01-01
影响因子：
4.4
通讯作者：
Ahmad, Ali
中科院分区：
文献类型：
--
作者：
Iannello, Alexandre;Boulassel, Mohamed-Rachid;Ahmad, Ali
IL-21是一种相对较新发现的免疫增强细胞因子，在控制慢性病毒感染中发挥重要作用。它主要由CD 4（+）T细胞产生，这也是HIV-1的主要目标，并且通常在HIV感染者中耗尽。因此，我们试图确定IL-21产生的动力学及其对CD 4（+）T细胞存活和HIV特异性CTL频率的潜在影响。为了这个目的，我们进行了一系列的横向和纵向研究，对不同群体的艾滋病毒感染的患者，并显示在这项研究中，细胞因子的生产是妥协的早期感染的过程中。感染者血清细胞因子浓度与CD 4（+）T细胞计数相关。在不同的HIV感染者群体中，只有精英控制者维持细胞因子的正常产生。高活性抗逆转录病毒疗法只能部分恢复这种细胞因子的产生。有趣的是，HIV感染的人CD 4（+）T细胞通过减少病毒感染细胞中c-Maf的表达来抑制细胞因子的产生，而不是在未感染的旁观者细胞中。我们还发现，在HIV感染的病毒血症患者中，产生IL-21的HIV特异性，但不是人CMV特异性，Ag经历的CD 4（+）T细胞的频率降低。此外，我们在这项研究中证明，重组人IL-21防止增强的HIV感染患者的CD 4（+）T细胞的自发性离体死亡。总之，我们的研究结果表明，血清IL-21浓度可以作为一个有用的生物标志物，用于监测HIV疾病的进展和细胞因子可以考虑在HIV感染患者的免疫治疗。免疫学杂志，2010，184：114-126。
IL-21 is a relatively newly discovered immune-enhancing cytokine that plays an essential role in controlling chronic viral infections. It is produced mainly by CD4(+) T cells, which are also the main targets of HIV-1 and are often depleted in HIV-infected individuals. Therefore, we sought to determine the dynamics of IL-21 production and its potential consequences for the survival of CD4(+) T cells and frequencies of HIV-specific CTL. For this purpose, we conducted a series of cross-sectional and longitudinal studies on different groups of HIV-infected patients and show in this study that the cytokine production is compromised early in the course of the infection. The serum cytokine concentrations correlate with CD4(+) T cell counts in the infected persons. Among different groups of HIV-infected individuals, only elite controllers maintain normal production of the cytokine. Highly active antiretroviral therapy only partially restores the production of this cytokine. Interestingly, HIV infection of human CD4(+) T cells inhibits cytokine production by decreasing the expression of c-Maf in virus-infected cells, not in uninfected bystander cells. We also show that the frequencies of IL-21-producing HIV-specific, but not human CMV-specific, Ag-experienced CD4(+) T cells are decreased in HIV-infected viremic patients. Furthermore, we demonstrate in this study that recombinant human IL-21 prevents enhanced spontaneous ex vivo death of CD4(+) T cells from HIV-infected patients. Together, our results suggest that serum IL-21 concentrations may serve as a useful biomarker for monitoring HIV disease progression and the cytokine may be considered for immunotherapy in HIV-infected patients. The Journal of Immunology, 2010, 184: 114-126.