Interleukin-10 plays an early role in generating virus-specific T cell anergy.
Interleukin-10 plays an early role in generating virus-specific T cell anergy.
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白细胞介素10在产生病毒特异性T细胞消音方面起着早期作用。
DOI：
10.1186/1471-2172-8-8
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发表时间：
2007-06-14
期刊：
影响因子：
3
通讯作者：
Jacob J
中科院分区：
文献类型：
--
作者：
Maris CH;Chappell CP;Jacob J
小鼠感染淋巴细胞性脉络丛脑膜炎病毒阿姆斯特朗株 (LCMVARM) 会产生强大的免疫反应和有效的病毒清除。这与变异株 LCMVClone13 的感染形成鲜明对比，后者会导致效应 T 细胞功能失活和病毒持续存在。 LCMVClone13 抑制抗病毒免疫反应并在宿主体内持续存在的机制尚不清楚。在这里，我们证明感染 LCMVClone13（而非 LCMVARM）会导致免疫抑制性细胞因子 IL-10 的血清水平稳定增加。在感染 LCMVClone13 的小鼠中注射中和单克隆抗体来阻断 IL-10，可在感染后 8 天显着增强效应 T 细胞反应。尽管IL-10阻断导致病毒滴度降低，但记忆T细胞的生成和维持仍然受到损害。感染后 30 天，IL-10 阻断的慢性感染小鼠中 CD8+ T 细胞的功能失活是不完全的，因为可以通过体外再刺激产生有效的 CTL（细胞毒性 T 淋巴细胞）。 IL-10敲除小鼠表现出类似的抗病毒CD8 T细胞反应模式：早期抗病毒T细胞显着增加，病毒水平下降；然而，IL-10 敲除小鼠中的 CD8 T 细胞最终也被激活，并且这些小鼠变得持续感染。我们的数据表明，IL-10 在 LCMVClone13 诱导的耐受性中发挥早期作用，尽管其他因素与 IL-10 协同诱导病毒特异性耐受性。
Infection of mice with the Armstrong strain of lymphocytic choriomeningitis virus (LCMVARM) leads to a robust immune response and efficient viral clearance. This is in contrast to infection with the variant strain LCMVClone13, which causes functional inactivation of effector T cells and viral persistence. The mechanism by which LCMVClone13 suppresses the antiviral immune response and persists in its host is unknown. Here we demonstrate that infection with LCMVClone13, but not with LCMVARM, resulted in a steady increase in the serum levels of the immuno-inhibitory cytokine, IL-10. Blockade of IL-10 using neutralizing monoclonal antibody injections in LCMVClone13-infected mice led to dramatically enhanced effector T cell responses at 8 days post-infection. Even though IL-10 blockade resulted in decreased viral titers, the generation and maintenance of memory T cells was still compromised. The functional inactivation of CD8+ T cells in IL-10-blocked, chronically infected mice 30 days post-infection was incomplete as potent CTL (cytotoxic T lymphocytes) could be generated by in vitro re-stimulation. IL-10 knockout mice showed a similar pattern of antiviral CD8 T cell responses: early antiviral T cells were dramatically increased and viral levels were decreased; however, CD8 T cells in IL-10 knockout mice were also eventually anergized and these mice became persistently infected. Our data suggest that IL-10 plays an early role in LCMVClone13-induced tolerance, although other factors collaborate with IL-10 to induce virus-specific tolerance.
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影响因子：
5.4
作者：
MATLOUBIAN, M;KOLHEKAR, SR;AHMED, R
通讯作者：
AHMED, R
DOI：
10.1098/rstb.2000.0637
发表时间：
2000-08-29
影响因子：
6.3
作者：
McMichael, AJ;Callan, M;Rowland-Jones, S
通讯作者：
Rowland-Jones, S
影响因子：
5.4
作者：
Smelt, SC;Borrow, P;Oldstone, MBA
通讯作者：
Oldstone, MBA
影响因子：
56.9
作者：
Ploegh, HL
通讯作者：
Ploegh, HL
影响因子：
64.8
作者：
Belkaid, Y;Piccirillo, CA;Sacks, DL
通讯作者：
Sacks, DL