Regulatory T cells control HIV replication in activated T cells through a cAMP-dependent mechanism
Regulatory T cells control HIV replication in activated T cells through a cAMP-dependent mechanism
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DOI：
10.1182/blood-2010-12-323162
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发表时间：
2011-05-19
期刊：
影响因子：
20.3
通讯作者：
Chougnet, Claire A.
中科院分区：
文献类型：
--
作者：
Moreno-Fernandez, Maria E.;Mauricio Rueda, Cesar;Chougnet, Claire A.
我们假设调节性T细胞（Tcons）可以通过控制常规T细胞（Tcons）中的HIV复制在HIV感染期间发挥有益作用。分别活化来自健康供体的纯化的Tcons和Tcons。用X4或R5 HIV毒株感染Tcons，并用或不用自体Tcons培养。Tcons和Tcons的共培养导致Tcon感染的剂量依赖性抑制，当使用1：1的Treg：Tcon比率时，这是显著的。Treg对HIV感染的抑制主要是通过接触依赖性机制介导的。细胞毒性T淋巴细胞相关抗原-4的阻断没有显著降低Treg功能。相反，Tcons通过cAMP依赖性机制发挥作用，因为Tcons中cAMP水平的降低、Tcons和Tcons之间间隙连接形成的阻断、CD 39活性的阻断以及Tcons中蛋白激酶A的阻断都消除了Treg介导的HIV复制抑制。我们的数据表明，在HIV感染过程中，THBG起着复杂的作用。虽然Tcons抑制特异性免疫应答，但它们对Tcons中HIV复制的抑制可能发挥有益作用，特别是在HIV感染早期，此时效应免疫细胞尚未激活。这种保护作用的THBE可能会对感染的结果产生深远的影响。（血。2011;117（20）：5372-5380）
We hypothesized that regulatory T cells (Tregs) could play a beneficial role during HIV infection by controlling HIV replication in conventional T cells (Tcons). Purified Tregs and Tcons from healthy donors were activated separately. Tcons were infected with the X4 or R5 HIV strains and cultured with or without autologous Tregs. Coculture of Tcons and Tregs resulted in a dose-dependent inhibition of Tcon infection, which was significant when a 1:1 Treg:Tcon ratio was used. Treg suppression of HIV infection was largely mediated by contact-dependent mechanisms. Blockage of cytotoxicT- lymphocyte-associated antigen-4 did not significantly reduce Treg function. In contrast, Tregs acted through cAMP-dependent mechanisms, because the decrease of cAMP levels in Tregs, the blockade of gap junction formation between Tregs and Tcons, the blockage of CD39 activity, and the blockage of protein kinase A in Tcons all abolished Treg-mediated suppression of HIV replication. Our data suggest a complex role for Tregs during HIV infection. Although Tregs inhibit specific immune responses, their inhibition of HIV replication in Tcons may play a beneficial role, particularly during early HIV infection, when the effector immune cells are not yet activated. Such a protective role of Tregs could have a profound impact on infection outcome. (Blood. 2011;117(20):5372-5380)