HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS
HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS
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DOI：
10.1182/blood-2006-05-021576
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发表时间：
2006-12-01
期刊：
影响因子：
20.3
通讯作者：
Chougnet, Claire
中科院分区：
文献类型：
--
作者：
Nilsson, Jakob;Boasso, Adriano;Chougnet, Claire
调节性T （Treg）细胞在人类免疫缺陷病毒（HIV）感染个体的淋巴组织中积累，导致免疫系统无法控制病毒复制。我们在此研究了未经治疗的进行性或非进行性疾病感染宿主（hiv感染的人类和猴免疫缺陷病毒[SIV]感染的猕猴）淋巴组织中的treg细胞数量和功能标记（FOXP3, CTLA-4， IDO和tgf - β 1）。我们发现，FOXP3(+) T细胞数量的增加以及treg细胞相关功能标记物的表达增加仅在疾病进展期间被检测到。这种增加与免疫激活无关。重要的是，高perforin/FOXP3比值与非进展性疾病相关，这表明病毒复制的免疫控制代表了细胞介导的免疫应答和treg细胞介导的这种应答的反向调节之间的平衡。此外，利用Treg细胞-HIV相互作用的体外模型，我们发现Treg细胞暴露于HIV通过cd4 -gp120依赖途径选择性地促进了它们的存活，从而为Treg细胞在病毒复制活跃的感染宿主中积累提供了潜在的机制。综上所述，我们的研究结果表明，治疗性操纵treg细胞数量和/或功能可以改善HIV感染的免疫控制。
Regulatory T (Treg) cells accumulate in the lymphoid tissues of human immunodeficiency virus (HIV)-infected individuals, contributing to the inability of the immune System to control virus replication. We investigate here Treg-cell numbers and functional markers (FOXP3, CTLA-4, IDO, and TGF-beta 1) in lymphoid tissues from untreated infected hosts with progressive or nonprogressive disease (HIV-infected humans and simian immunodeficiency virus [SIV]-infected macaques). We found that increased numbers of FOXP3(+) T cells as well as increased expression of Treg-cell-associated functional markers were detected only during progressive disease. Such increases were not correlated with immune activation. Of importance, a high-perforin/FOXP3 ratio was associated with nonprogressive disease, suggesting that the immune control of virus replication represents a balance between cell-mediated immune responses and Treg-cell-mediated counter regulation of such responses. Furthermore, using an in vitro model of Treg-cell-HIV interactions, we showed that exposure of Treg cells to HIV selectively promoted their survival via a CD4-gp120-dependent pathway, thus providing an underlying mechanism for the accumulation of Treg cells in infected hosts with active viral replication. Considered together, our findings imply that therapeutic manipulation of Treg-cell number and/or function could improve immune control of HIV infection.