IL-4-dependent Th2 collateral priming to inhaled antigens independent of toll-like receptor 4 and myeloid differentiation factor 88
IL-4-dependent Th2 collateral priming to inhaled antigens independent of toll-like receptor 4 and myeloid differentiation factor 88
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DOI：
10.4049/jimmunol.172.7.4527
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发表时间：
2004-04-01
影响因子：
4.4
通讯作者：
Bottomly, K
中科院分区：
文献类型：
--
作者：
Eisenbarth, SC;Zhadkevich, A;Bottomly, K
过敏性哮喘是一种炎症性肺部疾病，被认为是由对环境 Ag 做出反应的 2 型辅助 T 细胞引发和引导的。过敏原诱导 Th2 适应性免疫反应的机制尚不清楚，尽管现在已经清楚需要先天免疫信号来促进 DC 激活和 Th2 对吸入蛋白的敏化。然而，持续的 Th2 炎症（如慢性哮喘中所见）对幼稚淋巴细胞激活的影响尚未被探索。人们注意到，患有特应性疾病的患者对新过敏原产生敏感性的风险增加。这表明来自适应性免疫反应的信号可能促进对新抗原的敏化。我们使用Th2过继性哮喘转移小鼠模型来确定一种称为“附带启动”的新机制，其中幼稚CD4(+) T细胞被适应性而非先天免疫信号激活。 Th2 对新遇到的 Ag 的启动依赖于转移的 Th2 群体产生的 IL-4，但独立于 Toll 样受体 4 信号传导和骨髓分化因子 88 Toll 样受体信号传导途径。这些结果确定了一种新的 T 细胞启动机制，其中 Ag 特异性适应性免疫反应在缺乏经典先天免疫系统触发信号的情况下启动不同的 Ag 特异性 T 细胞反应。
Allergic asthma is an inflammatory lung disease thought to be initiated and directed by type 2 helper T cells responding to environmental Ags. The mechanisms by which allergens induce Th2-adaptive immune responses are not well understood, although it is now clear that innate immune signals are required to promote DC activation and Th2 sensitization to inhaled proteins. However, the effect of ongoing Th2 inflammation, as seen in chronic asthma, on naive lymphocyte activation has not been explored. It has been noted that patients with atopic disorders demonstrate an increased risk of developing sensitivities to new allergens. This suggests that signals from an adaptive immune response may facilitate sensitization to new Ags. We used a Th2-adoptive transfer murine model of asthma to identify a novel mechanism, termed "collateral priming," in which naive CD4(+) T cells are activated by adaptive rather than innate immune signals. Th2 priming to newly encountered Ags was dependent on the production of IL-4 by the transferred Th2 population but was independent of Toll-like receptor 4 signaling and the myeloid differentiation factor 88 Toll-like receptor signaling pathway. These results identify a novel mechanism of T cell priming in which an Ag-specific adaptive immune response initiates distinct Ag-specific T cell responses in the absence of classical innate immune system triggering signals.