Basic studies on adaptation the immune therapy to the patients with periodontal diseases by using synthetic peptides as an immunogen

以合成肽为免疫原对牙周病患者进行免疫治疗的基础研究

基本信息

批准号：
09470425
负责人：
MURAYAMA Yoji
金额：
$ 7.68万
依托单位：
Okayama university
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470425/
关键词：
Porphyromonas gingivalis 53kDa outer membrane protein T cell epitopes HLA class II Cytokines 免疫療法 Porphyromonas gingiralis 歯周病ヘルパパーT細胞 HLA classII リンフォカイン

项目摘要

As the first trial to adapt the immune therapy to the patients with periodontal diseases, we estimated how Ag53 is recognized by host immune cells and derive subsequent effector functions. We determined major T cell epitopes of Ag53 in EOP patients, and estimated them from the viewpoint of the restriction of HLA class II molecules. The results of this study are as follows.(1)We established Ag53 specific short-termed T cell lines from 22 subjects including 6 EOP patients and 16 healthy donors, using overlapping peptides based on Ag53 amino acid sequences. We found that all T cell lines from active EOP patients recognized common region (pl4l-p18l) on Ag53, while those of healthy donors showed heterogeneous specificity(2)Anti-DRBL monoclonal antibody inhibited Ag53-induced proliferation of most of the T cell lines.(3)A large amount of IFN-gamma was produced from all of established Th cell lines. The other cytokine production, including IL-4, 5, 6 and 10, were different among the Th cell lines.(4)The effect of the cytokine-profile produced from Th cells on the lgG production from B cells was evaluated. The Th cell lines producing high amount of Th2 type cytokines against Thl cytokines induced high IgG production. But the Th cell lines, which produced low Th2 cytokines against Thl cytokines. Did not induce the IgG production.(5)A larger amount of IL-5 from Th cells was detected in the culture with IgG production. compared to the culture without IgG production.These results suggest that AA residues from 14 1 to 181 is supposed to include major T cell epitope on Ag53 for active EOP patients but not for healthy individuals or inactive EOP patients. which might be interested in the establishment of the immune therapy for P gingivalisx infection in periodontal diseases

作为第一次调整免疫治疗对牙周疾病患者的试验，我们估计了AG53是如何通过宿主免疫细胞识别的，并得出了随后的效应子功能。我们确定了EOP患者AG53的主要T细胞表位，并从HLA II类分子的限制的角度估算了它们。这项研究的结果如下。（1）我们使用基于AG53氨基酸序列的重叠肽建立了来自22名受试者，包括6名EOP患者和16位健康供体的AG53特定的短期T细胞系。我们发现，来自AG53上公共区域（PL4L-P18L）的所有T细胞系都在AG53上识别出，而健康的供体的所有T均显示出异质的特异性（2）抗DRBL单克隆抗体抑制AG53诱导的大多数T细胞系的增殖。在TH细胞系中，包括IL-4、5、6和10在内的其他细胞因子产生不同。（4）评估了TH细胞从TH细胞产生的细胞因子核能对B细胞LGG产生的影响。针对THL细胞因子产生大量Th2型细胞因子的TH细胞系诱导高IgG产生。但是TH细胞系对THL细胞因子产生低的Th2细胞因子。没有诱导IgG产生。（5）在IgG产生的培养物中检测到TH细胞的大量IL-5。与没有IgG产生的培养物相比，这些结果表明，AA残基14 1至181应包括活跃EOP患者AG53上的主要T细胞表位，但不适合健康的个体或不活跃的EOP患者。可能对牙周疾病中P牙龈感染的免疫治疗感兴趣