PD-1 and CTLA-4 inhibitory cosignaling pathways in HIV infection and the potential for therapeutic intervention.
PD-1 and CTLA-4 inhibitory cosignaling pathways in HIV infection and the potential for therapeutic intervention.
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DOI：
10.4049/jimmunol.0803771
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发表时间：
2009-05-15
期刊：
影响因子：
--
通讯作者：
Walker BD
中科院分区：
文献类型：
--
作者：
Kaufmann DE;Walker BD
促炎机制和抑制过度免疫激活之间的平衡对于成功清除病原体而不损害宿主至关重要。特别是，B7：CD28家族的分子在调节T细胞活化和外周免疫耐受中起着关键作用。像HIV这样的慢性病原体，其特征是尽管可检测到病毒特异性T细胞反应，但仍在进行病毒复制，癌症细胞利用这些途径来减弱抗原特异性T细胞免疫。本文综述了B7：CD28家族分子PD-1、CTLA-4及其配体在人类HIV感染相关的病毒特异性T细胞衰竭和猕猴SIV模型中发挥积极和可逆作用的证据。我们讨论了基于对这些抑制网络的操纵进行免疫治疗干预的可能性，在动物模型中阻断PD-1通路所获得的有希望的数据，以及对这种治疗的挑战。
The balance between proinflammatory mechanisms and dampening of excessive immune activation is critical for successful clearance of a pathogen without harm to the host. In particular, molecules of the B7:CD28 family play a critical role in regulating T cell activation and peripheral tolerance. Chronic pathogens like HIV, which is characterized by ongoing viral replication in spite of detectable virus-specific T cell responses, and cancer cells have exploited these pathways to attenuate antigen-specific T cell immunity. This review summarizes evidence that the molecules of the B7:CD28 family PD-1, CTLA-4 and their ligands play an active and reversible role in virus- specific T cell exhaustion associated with HIV infection in humans and in the SIV model in macaques. We discuss the potential for immunotherapeutic interventions based on manipulation of these inhibitory networks, the promising data obtained with blockade of the PD-1 pathway in animal models, and the challenges to such therapies.
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