Ovalbumin-specific IgE modulates ovalbumin-specific T-cell response after repetitive oral antigen administration

Ovalbumin-specific IgE modulates ovalbumin-specific T-cell response after repetitive oral antigen administration
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DOI:
10.1016/j.jaci.2004.12.1121
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发表时间:
2005-04-01
影响因子:
14.2
通讯作者:
Mayumi, M
Mayumi, M
中科院分区:
医学1区
文献类型:
--
作者:
Omata, N;Ohshima, Y;Mayumi, M

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背景:有些患者即使血清抗原特异性IgE水平仍然很高,但随着年龄的增长,他们的食物过敏症状消失了。目的:为了阐明T细胞在抗原特异性IgE存在下的食物过敏中的作用,我们追踪了口服抗原administration.Methods后的抗原特异性T细胞应答:卵清蛋白(OVA)特异性T细胞受体(TCR)和OVA特异性IgE转基因(Tg)小鼠(OVA-TCR/IgE-Tg)和OVA特异性TCR Tg(OVA-TCR-Tg)小鼠每隔一天用高剂量的OVA或PBS喂养。给药7次后,分析脾、肠系膜淋巴结和派伊尔集合淋巴结的单个核细胞的OVA特异性增殖和细胞因子产生以及脾CD 4(+)CD 25(+)T细胞的数量。如果不施用OVA,来自OVA-TCR/IgE-Tg小鼠的脾细胞比来自OVA-TCR/IgE-Tg小鼠的脾细胞表现出更高的增殖反应,并产生更多的IL-4和IL-10以及更少的IFN-γ。Tg小鼠。与PBS喂养的小鼠相比,OVA喂养的OVA-TCR/IgE-Tg小鼠或OVA-TCR-Tg小鼠的脾细胞的增殖反应显著降低。OVA喂养小鼠脾脏中OVA特异性TCR(+)T细胞的数量减少,而CD 4 + CD 25 + T细胞的数量增加。结论:OVA特异性IgE的存在可调节OVA特异性脾细胞的增殖反应。不考虑OVA特异性IgE的存在,反复口服OVA诱导耐受,其似乎由克隆缺失/无反应性和TGF-β 1介导的主动抑制组成。
Background: Some patients outgrow their food allergies even though their serum antigen-specific IgE levels remain high. Objective: To elucidate the role of T cells in outgrowing food allergies in the presence of antigen-specific IgE, we tracked antigen-specific T-cell responses after oral antigen administration.Methods: Ovalbumin (OVA)-specific T-cell receptor (TCR) and OVA-specific IgE transgenic (Tg) mice (OVA-TCR/IgE-Tg) and OVA-specific TCR Tg (OVA-TCR-Tg) mice were fed with high doses of OVA or, PBS every other day. After 7 administrations, OVA-specific proliferation and cytokine production of mononuclear cells of the spleen, mesenteric lymph nodes, and Peyer's patches and the number of splenic CD4(+)CD25(+) T cells were analyzed.Results: Without OVA administration, the splenocytes from OVA-TCR/IgE-Tg mice exhibited a higher proliferative response and produced more IL-4 and IL-10 and less IFN-gamma than those from OVA-TCR-Tg mice. The proliferative responses of the splenocytes from either OVA-TCR/IgE-Tg mice or OVA-TCR-Tg mice fed with OVA were significantly reduced compared with those from PBS-fed mice. The number of OVA-specific TCR(+) T cells decreased in the spleen from OVA-fed mice, whereas the number of CD4+CD25+ T cells increased. The suppressed proliferation of splenocytes of OVA-fed mice was partially resumed by neutralization of TGF-beta 1, but not of IL-10.Conclusion: The presence of OVA-specific IgE modulated the OVA-specific responses of the splenocytes. Irrespective of the presence of OVA-specific IgE, repetitive oral administration of OVA induced tolerance, which seems to be composed of clonal deletion/anergy and TGF-beta 1-mediated active suppression.