Chemical-induced modification of oral immune tolerance in association with excess immunity

化学诱导的口腔免疫耐受性改变与过度免疫相关

基本信息

批准号：
12672176
负责人：
OHSAWA Motoyasu
金额：
$ 1.98万
依托单位：
Teikyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

Immune tolerance is a defense mechanism against induction of hyperimmune response like oral allergy, and the tolerance can be impaired by environmental chemicals. This research was undertaken to study a mechanism for chemical-induction of undesired antibody production through impairment of oral immune tolerance. For the purpose, the study was planed first to establish an oral tolerance model of mice, second to examine if the tolerance can be modified by some chemicals such as cyclqphosphamide (CP), estradiol (E2) and phenanthrene (PT), and to analyze mechanisms of their modification of the tolerance. Results were as follows :1. A mouse model of oral tolerance was established by use of ovalbumin (OVA) as an antigen. Female BALB/c mice given an oral administration of OVA resulted in stable tolerance of antibody production against OVA, that was effective to both Th1 and Th2 cell functions.2. In this model, chemicals such as CP, E2 and PT at high dose and given with oral OVA promoted production of antibodies against OVA and turned the tolerance less effective. The modification of the tolerance was characterized by preferable induction of IgG1 and further suppression of IgG2a against OVA, meaning dominant Th2 function.3. PT that promoted production of anti-OVA IgG1 dose-dependently preferably inhibit production of IFN-y rather than that of IL-4 in spleen cell cultures. Cultured spleen cells from the model mice of the tolerance given PT also gave less production of IFN-y compared with IL-4.These findings indicate that PT promoted excess production of antibodies via Th2 cell activation by modification of oral immune tolerance. It is also suggested that chemical-induction of hyperimmune response including allergy can be caused by such mechanism.

免疫耐受性是一种防御机制，可以防止诱导口服过敏这样的过度免疫反应，并且环境化学物质可能会损害耐受性。进行了这项研究，以研究通过口服免疫耐受性损害不希望的抗体产生的化学诱导机制。为此，首先计划了该研究以建立小鼠的口服耐受性模型，其次要检查耐受性是否可以通过某些化学物质（例如环磷酰胺（CP），雌二醇（E2）和势素（PT）（PT）进行修饰，并分析其耐受性修饰机制。结果如下：1。通过使用椭圆蛋白（OVA）作为抗原，建立了口服耐受性的小鼠模型。雌性BALB/c小鼠口服OVA给予了对OVA的抗体产生稳定性，这对Th1和Th2细胞功能都是有效的。2。在该模型中，高剂量的CP，E2和PT等化学物质促进了针对OVA的抗体产生，并使耐受性降低。耐受性的修饰的特征在于优选地诱导IgG1并进一步抑制IgG2a对OVA的抑制，这意味着主要的Th2功能3。 PT促进了抗OVA IgG1剂量依赖性依赖性的生产优选抑制IFN-Y的产生，而不是脾细胞培养物中IL-4的产生。与IL-4相比，来自耐受性的模型小鼠的培养的脾细胞也给出了IFN-Y的产生较少。还提出，包括过敏在内的超免疫反应的化学诱导可能是由这种机制引起的。