IFN-λ exerts opposing effects on T cell responses depending on the chronicity of the virus infection.
IFN-λ exerts opposing effects on T cell responses depending on the chronicity of the virus infection.
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DOI：
10.4049/jimmunol.1301705
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发表时间：
2014-04-15
期刊：
影响因子：
--
通讯作者：
Whitmire JK
中科院分区：
文献类型：
--
作者：
Misumi I;Whitmire JK
干扰素-λ可在多种细胞类型中诱导抗病毒状态，并可能有助于感染后的整体炎症环境。这两种效应都可能影响获得性免疫反应，但3型干扰素在初级和记忆性T细胞对感染反应的发展中的作用尚未得到评估。在此，我们检测了干扰素-λR1缺陷小鼠对急性或持续性淋巴细胞性脉络膜脑膜炎病毒感染的T细胞反应。在急性感染后，我们发现与WT Balb/c小鼠相比，干扰素-λR1缺陷小鼠产生了正常水平的干扰素，强大的NK细胞反应，但高于正常的CD4+和CD8+T细胞反应。有更多的T细胞是IL-7RHI，相应地，干扰素-λR缺陷小鼠的记忆T细胞数量增加了2-3倍。干扰素-λR表达的抑制作用不依赖于细胞因子直接进入T细胞。与急性感染相比，干扰素-λR缺陷小鼠产生的T细胞反应明显减弱，当面对高度传播的巨细胞病毒变种时，与WT小鼠相比体重减轻得更多。这些数据表明，干扰素-λR限制了短暂感染后的T细胞反应和记忆，但在持续感染期间增强了T细胞反应。因此，干扰素-λ受体的免疫调节功能是复杂的，并且随着整个炎症环境的不同而不同。
IFN-lambda (IFN-λ) induces an antiviral state in many cell types and may contribute to the overall inflammatory environment following infection. Either of these effects may influence adaptive immune responses, but the role of type-3 interferons in the development of primary and memory T cell responses to infection has not been evaluated. Herein, we examined T cell responses to acute or persistent lymphocytic choriomeningitis virus (LCMV) infection in IFN-λR1-deficient mice. Following acute infection, we find that IFN-λR1-deficient mice produced normal levels of interferon, robust NK cell responses, but greater than normal CD4+ and CD8+ T cell responses compared to WT Balb/c mice. There were more T cells that were IL-7Rhi and, correspondingly, the IFN-λR-deficient mice showed a 2–3-fold increase in memory T cell number. The inhibitory effect of IFN-λR expression was independent of direct cytokine signaling into T cells. In contrast to acute infection, the IFN-λR-deficient mice generated markedly diminished T cell responses and had greater weight loss compared to WT mice when confronted with a highly disseminating variant of LCMV. These data indicate that IFN-λR limits T cell responses and memory following transient infection but augments T cell responses during persisting infection. Thus, the immune regulatory functions for IFN-λR are complex and vary with the overall inflammatory environment.
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DOI：
10.1073/pnas.0811139106
发表时间：
2008-12-23
影响因子：
11.1
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