Omata Nemuko, Ohshima Yusei, Yasutomi Motoko, Yamada Akiko, Karasuyama Hajime, Mayumi Mitsufumi
Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, 2303 Shimoaizuki, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, USA.
J Allergy Clin Immunol. 2005 Apr;115(4):822-7. doi: 10.1016/j.jaci.2004.12.1121.
Some patients outgrow their food allergies even though their serum antigen-specific IgE levels remain high.
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.
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.
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.
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.
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。
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。
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。
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。
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。