Evaluation of immunological paradigms in a virus model: Are dendritic cells critical for antiviral immunity and viral clearance?
Evaluation of immunological paradigms in a virus model: Are dendritic cells critical for antiviral immunity and viral clearance?
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DOI：
10.4049/jimmunol.177.1.492
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发表时间：
2006-07-01
影响因子：
4.4
通讯作者：
Steel, Christina
中科院分区：
文献类型：
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作者：
Ciavarra, Richard P.;Stephens, Amber;Steel, Christina
我们使用转基因小鼠模型(CD11c-白喉毒素(DT)受体GFP)检测了树突状细胞(DC)在抗病毒免疫反应和病毒清除中的作用，该模型允许在体内有条件地去除树突状细胞(DC)。在转基因仔鼠中，DT可以系统地去除常规的和产生干扰素的血浆细胞样树突状细胞(PDC)，但不能系统地去除非转基因仔鼠的血浆细胞样树突状细胞(PDC)，而不消除脾巨噬细胞。出乎意料的是，在DC耗竭的小鼠中，早期(感染后12和48小时)水泡性口炎病毒的病毒清除是正常的，尽管血清I型干扰素效价显著降低。DC耗尽的小鼠仍然没有感染病毒，除了一个亚组(类似30%)在感染后6天出现压倒性和致命性的脑部感染。然而，DT治疗深刻地抑制了幼稚CD8(+)水泡性口炎病毒特异性T细胞的克隆性增殖，而不改变主要的Th1和Th2细胞因子反应。最佳克隆。尽管Th1/Th2细胞因子的产生没有改变，但扩增需要pDC，因为在体内用耗竭的抗体选择性地消除这些细胞也抑制了四聚体(+)细胞的扩张。总而言之，这些数据表明，传统的DC和pDC在较小程度上对幼稚的抗病毒T细胞的增殖至关重要。然而，在缺乏DO的情况下，初级适应性免疫反应的其他组成部分(Th1/Th2细胞因子)基本上是正常的，这可能是DC耗竭小鼠有效清除病毒的原因。因此，免疫系统中存在足够的冗余，以维持有效的病毒清除，尽管APC的丢失被认为是诱导初级抗病毒免疫反应所必需的。
We have examined the role of dendritic cells (DCs) in the antiviral immune response and viral clearance using a transgenic mouse model (CD11c-diphtheria toxin (DT) receptor GFP) that allows for their conditional ablation in vivo. DT administration systemically ablated conventional and IFN-producing plasmacytoid DCs (pDCs) in transgenic, but not nontransgenic littermates, without elimination of splenic macrophages. Unexpectedly, early (12 and 48 h postinfection) viral clearance of vesicular stomatitis virus was normal in DC-depleted mice despite markedly reduced serum titers of type I IFN. DC-depleted mice remained virus-free with the exception of a subset (similar to 30%) that developed overwhelming and fatal brain infections 6 days postinfection. However, DT treatment profoundly inhibited clonal expansion of naive CD8(+) vesicular stomatitis virus-specific T cells without altering the primary Th1 and Th2 cytokine response. Optimal clonal. expansion required pDCs because selective elimination of these cells in vivo with a depleting Ab also suppressed expansion of tetramer(+) cells, although Th1/Th2 cytokine production remained unaltered. Collectively, these data indicate that conventional DCs and to a lesser extent pDCs are critical for proliferation of naive antiviral T cells. However, other components of the primary adaptive immune response (Th1/Th2 cytokines) are essentially normal in the absence of DO, which may account for the efficient viral clearance seen in DC-depleted mice. Thus, sufficient redundancy exists in the immune system to sustain efficient viral clearance despite loss of an APC considered essential for induction of a primary antiviral immune response.