Allergen-derived T cell peptide-induced late asthmatic reactions precede the induction of antigen-specific hyporesponsiveness in atopic allergic asthmatic subjects
Allergen-derived T cell peptide-induced late asthmatic reactions precede the induction of antigen-specific hyporesponsiveness in atopic allergic asthmatic subjects
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DOI：
10.4049/jimmunol.167.3.1734
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发表时间：
2001-08-01
影响因子：
4.4
通讯作者：
Larché, M
中科院分区：
文献类型：
--
作者：
Oldfield, WLG;Kay, AB;Larché, M
变应原衍生肽可以诱导幼稚和Ag致敏小鼠的T细胞耐受。这之前是短暂的T细胞活化。在人类中，皮内注射短变应原衍生的T细胞肽表位在致敏受试者中引起IgE非依赖性孤立晚期哮喘反应（LARs）。在这项研究中，我们确定是否，在小鼠模型中，这样的肽产生低反应性与肽，或整个过敏原，无论是在临床上或在体外T细胞反应的再挑战。我们发现，第二次注射猫过敏原（Fel d 1）衍生的T细胞肽与LAR的显著减少或不存在相关，并且需要长达40周才能恢复到基线值。对整个猫皮屑的皮肤晚期反应也受到抑制，即使在没有经历初始LAR的受试者中也是如此。这些观察结果与肽和全变应原诱导的PBMC增殖以及培养物中IL-4、IL-13和IFN-γ的产生显著减少相关。因此，变应原衍生肽诱导对靶器官（肺）中后续肽注射的耐受性，降低对整个变应原的晚期皮肤反应性，并改变体外T细胞反应性。
Allergen-derived peptides can induce T cell tolerance in naive and Ag-primed mice. This is preceded by transient T cell activation. In humans, intradermal administration of short allergen-derived T cell peptide epitopes provokes IgE-independent isolated late asthmatic reactions (LARs) in sensitized subjects. In this study, we determine whether, as in mouse models, such peptides produce hyporesponsiveness to rechallenge with peptides, or whole allergen, either clinically or in terms of in vitro T cell responses. We found that a second injection of cat allergen (Fel d 1)-derived T cell peptides was associated with a marked reduction, or absence, of the LAR, and that up to 40 wk was required for return to baseline values. The cutaneous late-phase reaction to whole cat dander was also inhibited, even in subjects who did not experience an initial LAR. These observations were associated with a significant decrease in peptide- and whole allergen-induced proliferation of PBMCs and the production of IL-4, IL-13, and IFN-gamma in cultures. Thus, allergen-derived peptides induce tolerance to subsequent peptide injection in the target organ (the lung), reduce late-phase cutaneous responsiveness to whole allergen, and alter in vitro T cell reactivity.