Unique features of memory T cells in HIV elite controllers: a systems biology perspective
Unique features of memory T cells in HIV elite controllers: a systems biology perspective
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DOI：
10.1097/coh.0b013e32834589a1
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发表时间：
2011-05-01
影响因子：
4.1
通讯作者：
Sekaly, Rafick-Pierre
中科院分区：
文献类型：
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作者：
Fonseca, Simone G.;Procopio, Francesco A.;Sekaly, Rafick-Pierre
审查目的精英控制者是一群罕见的 HIV 感染者，他们控制 HIV 复制并在不接受抗逆转录病毒治疗 (ART) 的情况下维持正常的 CD4 细胞计数。人们对控制感染的机制知之甚少。本综述将重点关注利用系统生物学方法鉴定精英控制器中不同记忆 T 细胞亚群上调或下调的信号通路。还将重点介绍猿猴免疫缺陷病毒 (SIV) 自然宿主中记忆 T 细胞的特征。最后，我们将讨论这些方法将如何指导新疫苗和治疗干预措施的开发。最近的研究结果我们小组的研究确定了 FOXO3a、STAT5 和 Wnt/β-catenin 通路是与精英控制者中记忆 T 细胞的存活相关的独特分子特征。这些发现为设计预防 HIV 感染者 T 细胞耗竭的新策略开辟了道路。总结利用系统生物学来识别参与记忆 T 细胞存活的分子途径是了解精英控制者中 HIV 控制机制的有力工具。这将有助于确定免疫保护的相关性，从而设计有效的艾滋病毒疫苗和新的有针对性的治疗干预措施。
Purpose of reviewElite controllers constitute a rare group of HIV-infected individuals who control HIV replication and maintain normal CD4 cell counts without antiretroviral therapy (ART). The mechanisms involved in the control of infection are poorly understood. This review will focus on the identification of signaling pathways upregulated or downregulated in different memory T-cell subsets in elite controllers by using systems biology approaches. Features of memory T cells in simian immunodeficiency virus (SIV) natural hosts will be also highlighted. Finally, we will discuss how these approaches will guide the development of new vaccines and therapeutic interventions.Recent findingsStudies by our group identified the FOXO3a, STAT5, and Wnt/beta-catenin pathways as unique molecular signatures associated with survival of memory T cells in elite controllers. These discoveries open the path for the design of new strategies to prevent T-cell depletion in HIV-infected individuals.SummaryThe use of systems biology to identify molecular pathways involved in the survival of memory T cells is a powerful tool toward the understanding of mechanisms of HIV control in elite controllers. This will help to identify correlates of immune protection leading to the design of effective HIV vaccines and new targeted therapeutic interventions.