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在反复口服抗原给药后,卵清蛋白特异性IgE调节卵清蛋白特异性T细胞反应。

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

作者信息

Omata Nemuko, Ohshima Yusei, Yasutomi Motoko, Yamada Akiko, Karasuyama Hajime, Mayumi Mitsufumi

机构信息

Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, 2303 Shimoaizuki, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, USA.

出版信息

J Allergy Clin Immunol. 2005 Apr;115(4):822-7. doi: 10.1016/j.jaci.2004.12.1121.

Abstract

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-beta1, 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-beta1-mediated active suppression.

摘要

背景

一些患者虽血清抗原特异性IgE水平仍高,但食物过敏症状却消失了。

目的

为阐明在存在抗原特异性IgE的情况下T细胞在食物过敏症状消失中的作用,我们在口服抗原后追踪了抗原特异性T细胞反应。

方法

每隔一天给卵清蛋白(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)以及OVA特异性TCR Tg(OVA-TCR-Tg)小鼠喂食高剂量OVA或磷酸盐缓冲盐水(PBS)。7次给药后,分析脾脏、肠系膜淋巴结和派伊尔结中单核细胞的OVA特异性增殖和细胞因子产生情况以及脾脏CD4+CD25+T细胞的数量。

结果

未给予OVA时,OVA-TCR/IgE-Tg小鼠的脾细胞比OVA-TCR-Tg小鼠的脾细胞表现出更高的增殖反应,产生更多的白细胞介素-4(IL-4)和白细胞介素-10(IL-10),产生的干扰素-γ(IFN-γ)更少。与喂食PBS的小鼠相比,喂食OVA的OVA-TCR/IgE-Tg小鼠或OVA-TCR-Tg小鼠的脾细胞增殖反应均显著降低。喂食OVA小鼠脾脏中OVA特异性TCR+T细胞数量减少,而CD4+CD25+T细胞数量增加。通过中和转化生长因子-β1(TGF-β1)可部分恢复喂食OVA小鼠脾细胞受抑制的增殖,但中和白细胞介素-10则不能。

结论

OVA特异性IgE的存在调节了脾细胞的OVA特异性反应。无论是否存在OVA特异性IgE,重复口服OVA均可诱导耐受,这似乎由克隆清除/无反应性和TGF-β1介导的主动抑制组成。

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