Adaptive immune cells temper initial innate responses.
Adaptive immune cells temper initial innate responses.
复制标题
适应性免疫细胞缓和最初的先天反应。
作者：
Toll样受体（TLR）识别保守的微生物结构，称为病原体相关分子模式。来自TLR的信号传导导致共刺激分子的上调，以更好地引发T细胞和由先天免疫细胞分泌炎性细胞因子。缺乏淋巴细胞的宿主通常死于急性感染，可能是由于它们缺乏有效清除病原体的适应性免疫反应。然而，我们在这里表明，由于缺乏居住T细胞而释放的先天免疫反应也可能是死亡的直接原因。病毒感染或给药poly（I：C）（TLR 3的配体）导致T细胞或淋巴细胞缺陷小鼠以依赖于NK细胞和肿瘤坏死因子的方式发生细胞因子风暴。我们进一步表明，通过耗尽野生型小鼠中的CD 4+和CD 8+细胞以及将T淋巴细胞转移到Rag-1缺陷型小鼠中，T细胞对于缓和早期先天性反应是必要的和足够的。除了天然调节性T细胞的作用外，静息CD 4 + CD 25 − Foxp 3 −或CD 8 + T细胞与先天性细胞的密切接触也可以以抗原非依赖性方式抑制各种先天性细胞的细胞因子激增。因此，适应性免疫细胞在调节初始先天反应中具有意想不到的作用。本文的在线版本（doi：10.1038/nm 1633）包含补充材料，可供授权用户使用。
Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells. Lymphocyte-deficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4+ and CD8+ cells in wild-type mice and the transfer of T lymphocytes into Rag-1–deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4+CD25−Foxp3− or CD8+ T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses. The online version of this article (doi:10.1038/nm1633) contains supplementary material, which is available to authorized users.
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