Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression.
Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression.
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DOI：
10.1084/jem.20082901
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发表时间：
2009-07-06
期刊：
影响因子：
--
通讯作者：
Larché M
中科院分区：
文献类型：
--
作者：
Campbell JD;Buckland KF;McMillan SJ;Kearley J;Oldfield WL;Stern LJ;Grönlund H;van Hage M;Reynolds CJ;Boyton RJ;Cobbold SP;Kay AB;Altmann DM;Lloyd CM;Larché M
使用低剂量含有来自Fel d 1（主要猫过敏原）的T细胞表位的肽治疗过敏性哮喘患者，可降低过敏性致敏作用并改善疾病的替代标志物。在这里，我们证明了一个关键的免疫机制，连接表位抑制，与这种治疗效果。用来自单一过敏原的选定表位处理导致对同一分子内的其它（“连接的”）表位的应答的抑制。在人类哮喘受试者和一种新的HLA-DR 1转基因哮喘小鼠模型中，肽免疫治疗后诱导了这种现象。使用DR 1四聚体追踪过敏原特异性T细胞，确定抑制与白细胞介素（IL）-10+ T细胞的诱导相关，这些T细胞比对单一治疗肽特异性的T细胞更丰富，并且通过抗IL-10受体给药逆转。在该模型中，气道病理生理学的消退与变应原特异性Th 2细胞的募集、增殖和效应功能降低相关。我们的研究结果首次提供了在人类过敏性疾病和小鼠模型中相关表位抑制和IL-10诱导的体内证据，该小鼠模型旨在密切模拟人类的肽治疗。
Treatment of patients with allergic asthma using low doses of peptides containing T cell epitopes from Fel d 1, the major cat allergen, reduces allergic sensitization and improves surrogate markers of disease. Here, we demonstrate a key immunological mechanism, linked epitope suppression, associated with this therapeutic effect. Treatment with selected epitopes from a single allergen resulted in suppression of responses to other (“linked”) epitopes within the same molecule. This phenomenon was induced after peptide immunotherapy in human asthmatic subjects and in a novel HLA-DR1 transgenic mouse model of asthma. Tracking of allergen-specific T cells using DR1 tetramers determined that suppression was associated with the induction of interleukin (IL)-10+ T cells that were more abundant than T cells specific for the single-treatment peptide and was reversed by anti–IL-10 receptor administration. Resolution of airway pathophysiology in this model was associated with reduced recruitment, proliferation, and effector function of allergen-specific Th2 cells. Our results provide, for the first time, in vivo evidence of linked epitope suppression and IL-10 induction in both human allergic disease and a mouse model designed to closely mimic peptide therapy in humans.
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DOI：
10.1084/jem.191.2.265
发表时间：
2000-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lloyd CM;Delaney T;Nguyen T;Tian J;Martinez-A C;Coyle AJ;Gutierrez-Ramos JC
通讯作者：
Gutierrez-Ramos JC
影响因子：
15.3
作者：
Apostolou, I;von Boehmer, H
通讯作者：
von Boehmer, H
CD4+ CD25+调节T细胞体内转移后气道炎症和过度反应性的分辨率取决于白介素10。
DOI：
10.1084/jem.20051166
发表时间：
2005-12-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1084/jem.181.3.867
发表时间：
1995-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Altmann DM;Douek DC;Frater AJ;Hetherington CM;Inoko H;Elliott JI
通讯作者：
Elliott JI
影响因子：
4.4
作者：
Henry, Emmanuelle;Desmet, Christophe J.;Bureau, Fabrice
通讯作者：
Bureau, Fabrice