THE MOLECULAR MECHANISMS OF IMMUNE RESPONSE AND INTERACTION OF THE IMMUNE AND NERVOUS SYSTEMS IN FOOD ALLERGY

1. 用40个氨基酸取代的OVA323-339类似物刺激卵清蛋白（OVA323-339）残基323-339特异性T细胞受体（TCR）转基因（Tg）小鼠的T细胞，根据细胞因子分泌和诱导抗体产生的模式，可将其反应至少分为四种类型。通过改变用于兴奋剂的OVA323-339的剂量，也可以引起类似的分类反应。我们还在类似肽组中发现了能够抑制t细胞对OVA323-339反应的肽。在动物模型中，腹腔注射抑制肽可抑制食物过敏反应。2. 使用ova特异性TCR-Tg小鼠检测肠道免疫系统对口服过敏原的反应。ova喂养的TCR-Tg小鼠Peyer's patch细胞在抗原刺激下分泌ifn - γ和IL-5，上皮内淋巴细胞分泌ifn - γ。脾CD4 T细胞反应减弱，表明口服耐受。tcr结扎后，这些耐受性T细胞的Ca_<2+>动员受损。饲喂卵细胞可诱导淋巴结胸腺细胞和CD4 T细胞凋亡，并可部分消除p53缺陷小鼠的口服耐受。此外，还澄清了脾细胞和Peyer’s斑块细胞抗原呈递功能的差异。3. 利用小鼠胚胎脑细胞体外培养系统，研究了炎症因子对神经细胞反应的影响。因此，IL-6家族细胞因子和tgf - β家族细胞因子均可诱导神经祖细胞向胶质细胞分化。此外，炎症型NOS产生的一氧化氮以p53依赖的方式引发神经细胞凋亡。这些发现清楚地证明了炎症系统和神经系统之间的相互作用。

1. The response of T cells from transgenic(Tg)mice expressing T-cell receptor(TCR)specific for residues 323-339 of ovalbumin(OVA323-339)could be classified into at least four types according to the pattern of cytokine secretion and induction of antibody production, when a panel of 40 amino-acid substituted analogs of OVA323-339 was used as stimulations. The similarly classified response could be elicited by changing the dose of OVA323-339 used for stimulants. We also found peptides with ability to inhibit the T-cell response to OVA323-339 among the panel of analog peptides. Intraperitoneal administration of the inhibitory peptide could suppress food-allergic reaction in an animal model. 2. The response of the intestinal immune system to orally administrated allergen was examined using the OVA-specific TCR-Tg mice. Peyer's patch cells from OVA-fed TCR-Tg mice secreted IFN-gamma and IL-5 in response to antigen stimulation, and intraepithelial lymphocytes secreted IFN-gamma. The response of splenic CD4 T cells was diminished, indicative of oral tolerance. Ca_<2+> mobilization after TCR-ligation was impaired in these tolerant T cells. OVA feeding induced apoptosis of thymocytes and CD4 T cells in lymph nodes, and oral tolerance was partly abrogated in p53-deficient mice. In addition, the differences in antigen presentation functions between splenic cells and Peyer's patch cells were clarified. 3. The effect of inflammatory cytokines on neural cell response was estimated by an in vitro culture system using embryonic mouse brain cells. As a result, both IL-6 family cytokines and TGF-beta family cytokines induced glial differentiation of neural progenitor cells. In addition, nitric oxide produced by inflammatory type NOS triggered apoptosis of neural cells in a p53-dependent manner. These findings clearly demonstrate the interaction between inflammatory system and nervous system.