Regulatory T cells in retroviral infections.
Regulatory T cells in retroviral infections.
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DOI：
10.1371/journal.ppat.1006776
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发表时间：
2018-03
期刊：
影响因子：
6.7
通讯作者：
Dittmer U
中科院分区：
文献类型：
--
作者：
Hasenkrug KJ;Chougnet CA;Dittmer U
严格调节免疫反应不仅对预防自身免疫性疾病至关重要，而且对预防感染过程中的免疫病理损伤也至关重要，在感染过程中，过度活跃的免疫反应可能比病原体本身对宿主的危害更大。调节性T细胞（Tregs）在这种调节中起着关键作用，这是通过Friend逆转录病毒（FV）小鼠模型发现的。随后的FV研究揭示了Treg的基本生物学信息，包括它们对效应细胞的抑制活性以及病毒诱导Treg扩增的分子机制。Treg抑制不仅限制了免疫病理，而且还阻止了导致慢性感染的病原体的完全消除。因此，Tregs在持续性逆转录病毒感染的发病机制中起着复杂的作用。通过操纵Tregs来重新激活慢性病毒感染中的效应t细胞反应的新治疗概念也来自于FV模型的研究。这一认识引发了许多研究，以表征Tregs在人类HIV发病机制中的作用，其中一个复杂的画面正在出现。一方面，Tregs抑制hiv特异性效应T细胞反应，本身就是感染的靶标，但另一方面，Tregs抑制hiv诱导的免疫过度激活，从而减缓常规CD4+ T细胞的感染，限制免疫病理。在这篇综述中，FV小鼠模型的基本发现与HIV研究的临床和基础研究相结合。此外，还将讨论在猴免疫缺陷病毒（SIV）猴模型中进行的少数Treg研究。这篇综述全面介绍了Treg在不同逆转录病毒感染中的不同作用，以及通过操纵Treg应答来治疗逆转录病毒的慢性和发病机制的可能治疗方法。调节性T细胞（Tregs）在逆转录病毒感染中发挥着非常复杂的作用，在感染的急性和慢性阶段，Tregs的有益和有害影响的平衡可能会发生变化。因此，开发通过调节Tregs来治疗慢性逆转录病毒感染的疗法需要详细了解Tregs在特定感染的特定阶段的积极和消极作用。在这里，我们回顾了在逆转录病毒感染中启动和控制Treg反应的分子机制，以及由Treg在功能上操纵的靶细胞。启动这一研究领域的Friend逆转录病毒小鼠模型的基本发现与艾滋病毒研究的临床和基础研究相结合。靶向操纵Treg反应在增强对感染的免疫反应、疫苗反应以及慢性逆转录病毒感染的治愈或功能性治愈方面具有光明的前景。
Tight regulation of immune responses is not only critical for preventing autoimmune diseases but also for preventing immunopathological damage during infections in which overactive immune responses may be more harmful for the host than the pathogen itself. Regulatory T cells (Tregs) play a critical role in this regulation, which was discovered using the Friend retrovirus (FV) mouse model. Subsequent FV studies revealed basic biological information about Tregs, including their suppressive activity on effector cells as well as the molecular mechanisms of virus-induced Treg expansion. Treg suppression not only limits immunopathology but also prevents complete elimination of pathogens contributing to chronic infections. Therefore, Tregs play a complex role in the pathogenesis of persistent retroviral infections. New therapeutic concepts to reactivate effector T-cell responses in chronic viral infections by manipulating Tregs also came from work with the FV model. This knowledge initiated many studies to characterize the role of Tregs in HIV pathogenesis in humans, where a complex picture is emerging. On one hand, Tregs suppress HIV-specific effector T-cell responses and are themselves targets of infection, but on the other hand, Tregs suppress HIV-induced immune hyperactivation and thus slow the infection of conventional CD4+ T cells and limit immunopathology. In this review, the basic findings from the FV mouse model are put into perspective with clinical and basic research from HIV studies. In addition, the few Treg studies performed in the simian immunodeficiency virus (SIV) monkey model will also be discussed. The review provides a comprehensive picture of the diverse role of Tregs in different retroviral infections and possible therapeutic approaches to treat retroviral chronicity and pathogenesis by manipulating Treg responses. Regulatory T cells (Tregs) play a very complex role in retroviral infections, and the balance of beneficial versus detrimental effects from Tregs can change between the acute and chronic phase of infection. Therefore, the development of therapeutics to treat chronic retroviral infections via modulation of Tregs requires detailed information regarding both the positive and negative contributions of Tregs in a particular phase of a specific infection. Here, we review the molecular mechanisms that initiate and control Treg responses in retroviral infections as well as the target cells that are functionally manipulated by Tregs. Basic findings from the Friend retrovirus mouse model that initiated this area of research are put into perspective with clinical and basic research from HIV studies. The targeted manipulation of Treg responses holds a bright future for enhancing immune responses to infections, vaccine responses, and for cure or functional cure of chronic retroviral infections.
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影响因子：
3.8
作者：
Angin, Mathieu;King, Melanie;Addo, Marylyn M.
通讯作者：
Addo, Marylyn M.
DOI：
10.4049/jimmunol.1402699
发表时间：
2015-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Blackburn MJ;Zhong-Min M;Caccuri F;McKinnon K;Schifanella L;Guan Y;Gorini G;Venzon D;Fenizia C;Binello N;Gordon SN;Miller CJ;Franchini G;Vaccari M
通讯作者：
Vaccari M
影响因子：
4.4
作者：
Burchill, Matthew A.;Yang, Jianying;Farrar, Michael A.
通讯作者：
Farrar, Michael A.
影响因子：
4.4
作者：
Andersson, J;Boasso, A;Chougnet, CA
通讯作者：
Chougnet, CA
影响因子：
4.4
作者：
Cecchinato, Valentina;Tryniszewska, Elzbieta;Franchini, Genoveffa
通讯作者：
Franchini, Genoveffa