Regulatory CD4+Foxp3+ T cells control the severity of anaphylaxis.
Regulatory CD4+Foxp3+ T cells control the severity of anaphylaxis.
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DOI：
10.1371/journal.pone.0069183
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kaiserlian D
中科院分区：
文献类型：
--
作者：
Kanjarawi R;Dy M;Bardel E;Sparwasser T;Dubois B;Mecheri S;Kaiserlian D
过敏反应是一种对过敏原的速发型超敏反应，继发于过敏原特异性IgE引起的肥大细胞脱粒，危及生命。调节性T细胞（Treg）可以控制过敏性致敏和肥大细胞脱颗粒，但其对过敏性症状的临床益处记录甚少。在这里，我们研究了在过敏反应的效应臂中Treg的作用是否会导致过敏反应。我们使用了一种经验证的IgE介导的被动全身过敏反应模型，该模型通过DNP特异性IgE被动致敏小鼠中DNP-HSA静脉内激发诱导。通过体温下降以及血浆组胺和血清mMCP 1水平监测过敏反应。使用MHC II类缺陷（Aβ°/°）小鼠、用抗-CD 25或抗-CD 4 mAb处理以及DEREG小鼠中Foxp 3 + Treg的条件性消融来分析Treg的作用。还通过使用FoxP 3-eGFP敲入小鼠的转移实验来评估Treg的治疗功效。过敏反应没有发生在肥大细胞缺陷的W/Wv突变小鼠，只有中度和短暂的小鼠缺乏组胺受体-1。组成性Treg的缺陷，无论是遗传的还是由抗体或毒素治疗诱导的，都会导致更严重和/或持续的体温过低，与血清mMCP 1升高相关，但与组胺无关。在Treg缺陷的DEREG小鼠中，从未经处理的或DNP致敏的供体连续转移Foxp 3 + Treg同样减轻了体温下降。组成型Foxp 3 + Treg可以控制小鼠肥大细胞和IgE依赖性过敏反应的症状期。这可能开辟了新的治疗途径，使用组成性而不是Ag特异性Treg诱导过敏性患者的耐受性。
Anaphylaxis is a life-threatening outcome of immediate-type hypersensitivity to allergen, consecutive to mast cell degranulation by allergen-specific IgE. Regulatory T cells (Treg) can control allergic sensitization and mast cell degranulation, yet their clinical benefit on anaphylactic symptoms is poorly documented. Here we investigated whether Treg action during the effector arm of the allergic response alleviates anaphylaxis. We used a validated model of IgE-mediated passive systemic anaphylaxis, induced by intravenous challenge with DNP-HSA in mice passively sensitized with DNP-specific IgE. Anaphylaxis was monitored by the drop in body temperature as well as plasma histamine and serum mMCP1 levels. The role of Treg was analyzed using MHC class II-deficient (Aβ°/°) mice, treatment with anti-CD25 or anti-CD4 mAbs and conditional ablation of Foxp3+ Treg in DEREG mice. Therapeutic efficacy of Treg was also evaluated by transfer experiments using FoxP3-eGFP knock-in mice. Anaphylaxis did not occur in mast cell-deficient W/Wv mutant mice and was only moderate and transient in mice deficient for histamine receptor-1. Defects in constitutive Treg, either genetic or induced by antibody or toxin treatment resulted in a more severe and/or sustained hypothermia, associated with a rise in serum mMCP1, but not histamine. Adoptive transfer of Foxp3+ Treg from either naïve or DNP-sensitized donors similarly alleviated body temperature loss in Treg-deficient DEREG mice. Constitutive Foxp3+ Treg can control the symptomatic phase of mast cell and IgE-dependent anaphylaxis in mice. This might open up new therapeutic avenues using constitutive rather than Ag-specific Treg for inducing tolerance in allergic patients.
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影响因子：
7.3
作者：
Duarte J;Caridade M;Graca L
通讯作者：
Graca L
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：
10.4049/jimmunol.1102389
发表时间：
2012-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ganeshan K;Bryce PJ
通讯作者：
Bryce PJ
DOI：
10.1073/pnas.93.23.13316
发表时间：
1996-11-12
影响因子：
11.1
作者：
Inoue, I;Yanai, K;Watanabe, T
通讯作者：
Watanabe, T
影响因子：
32.4
作者：
Gri G;Piconese S;Frossi B;Manfroi V;Merluzzi S;Tripodo C;Viola A;Odom S;Rivera J;Colombo MP;Pucillo CE
通讯作者：
Pucillo CE