Allergen-responsive CD4+CD25+ regulatory T cells in children who have outgrown cow's milk allergy.

Allergen-responsive CD4+CD25+ regulatory T cells in children who have outgrown cow's milk allergy.
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DOI:
10.1084/jem.20032121
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发表时间:
2004-06-21
影响因子:
15.3
通讯作者:
Brandtzaeg, P
Brandtzaeg, P
中科院分区:
医学1区
文献类型:
--
作者:
Karlsson, MR;Rugtveit, J;Brandtzaeg, P

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儿童牛奶过敏通常持续时间较短,这使得这种疾病成为研究饮食抗原耐受性的有趣临床模型。在这里,我们研究了21名最初过敏的儿童的T细胞反应,这些儿童在>2个月的无奶期后,重新将牛奶引入他们的饮食中。与维持临床活动性过敏的儿童相比,过敏耐受儿童的循环CD 4 + CD 25 + T细胞频率较高,外周血单核细胞(PBMC)中对牛β-乳球蛋白的体外增殖反应降低。两组之间没有观察到多克隆促分裂原植物血凝素刺激的增殖活性的显着差异。耐受儿童PBMC中CD 25+细胞的耗竭导致体外抗β-乳球蛋白增殖增加5倍。这表明耐受性与循环中CD 4 + CD 25+调节性T(Treg)细胞的出现有关,这些细胞能够抑制再引入牛奶后1周产生的效应T细胞。CD 4 + CD 25 + Treg细胞的抑制功能显示部分细胞接触依赖性。总的来说,我们的研究提供了人类数据,表明粘膜诱导对饮食抗原的耐受性与CD 4 + CD 25 + Treg细胞的发育相关。
Cow's milk allergy in children is often of short duration, which makes this disorder an interesting clinical model for studies of tolerance to dietary antigens. Here, we studied T cell responses in 21 initially allergic children who, after a milk-free period of >2 mo, had cow's milk reintroduced to their diet. Children who outgrew their allergy (tolerant children) had higher frequencies of circulating CD4+CD25+ T cells and decreased in vitro proliferative responses to bovine β-lactoglobulin in peripheral blood mononuclear cells (PBMCs) compared with children who maintained clinically active allergy. No significant difference in proliferative activity stimulated by the polyclonal mitogen phytohemagglutinin was observed between the two groups. Depletion of CD25+ cells from PBMCs of tolerant children led to a fivefold increase in in vitro proliferation against β-lactoglobulin. This suggests that tolerance is associated with the appearance of circulating CD4+CD25+ regulatory T (Treg) cells that are capable of suppressing the effector T cells generated 1 wk after reintroduction of cow's milk. The suppressive function of the CD4+CD25+ Treg cells was shown to be partly cell contact dependent. Collectively, our study provides human data to suggest that mucosal induction of tolerance against dietary antigens is associated with the development of CD4+CD25+ Treg cells.
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