Inhibition of IL-2 induced IL-10 production as a principle of phase-specific immunotherapy
Inhibition of IL-2 induced IL-10 production as a principle of phase-specific immunotherapy
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DOI：
10.4049/jimmunol.177.7.4636
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发表时间：
2006-10-01
影响因子：
4.4
通讯作者：
Saha, Bhaskar
中科院分区：
文献类型：
--
作者：
Bodas, Manish;Jain, Nitya;Saha, Bhaskar
多诺瓦利什曼原虫是一种原生动物寄生虫，会导致一种致命的疾病——内脏利什曼病。抗利什曼T细胞反应的抑制。这种疾病的特征被认为是由于缺乏T细胞生长因子IL-2。我们证明，在多诺瓦氏L.感染后的第一周，IL-2诱导IL-10，在感染后14天抑制T细胞的宿主保护功能。在BALB/c小鼠中，观察到的抑制与CD4（+）糖皮质激素诱导的TNF受体（+）T细胞和Foxp3表达增加同时发生，暗示il -2依赖性调节性T细胞控制抗利什曼免疫反应。事实上，感染后不同时间点的IL-2和IL-10中和分别显示了它们在启动期和效应期的不同作用，并建立了正在进行的免疫反应的动力学调节作为合理的、阶段特异性免疫治疗的原则。
Leishmania donovani, a protozoan parasite, inflicts a fatal disease, visceral leishmaniasis. The suppression of antileishmanial T cell responses. that characterizes the disease was proposed to be due to deficiency of a T cell growth factor, IL-2. We demonstrate that during the first week after L. donovani infection, IL-2 induces IL-10 that suppresses the host-protective functions of T cells 14 days after infection. The observed suppression is concurrent with increased CD4(+)glucocorticoid-induced TNF receptor(+) T cells and Foxp3 expression in BALB/c mice, implicating IL-2-dependent regulatory T cell control of antileishmanial immune responses. Indeed, IL-2 and IL-10 neutralization at different time points after the infection demonstrates their distinct roles at the priming and effector phases, respectively, and establishes kinetic modulation of ongoing immune responses as a principle of a rational, phase-specific immunotherapy.