T CELL REGULATION OF CARIES IMMUNITY/PERIODONTAL DISEASE

T 细胞对龋齿免疫/牙周病的调节

基本信息

批准号：
3072192
负责人：
HIROSHI KIYONO
金额：
$ 6.8万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-07-01 至 1993-06-30
项目状态：
已结题

项目摘要

Compelling evidence has been presented that immunobiological interactions are very important in development and prevention of the two major oral diseases, i.e., periodontal disease and dental caries. For example, polyclonal and antigen-specific immune responses to periodontopathoges, e.g., Bacteroides gingivalis (Bg) and Haemophilis actinomycetemcomitans (Ha) play important roles in the development of gingival tissue destruction in periodontal diseases. It has also been shown that oral administration of Streptococcus mutans vaccine to human induces antigen-specific secretory IgA (S-IgA) responses in mucosal associated secretions including saliva, tears, colostrum and mucus secretions of the gastrointestinal and upper respiratory tracts, and that antigen-specific IgA producing cell appear in the peripheral circulation prior to IgA responses in these external secretions presumably as a part of the common mucosal immune system. However, very little is known about regulatory mechanisms, especially T cell involvement in these immune responses. In this regard, the overall goal of this grant proposal is to study the cellular and molecular aspects of T cell regulation of immune responses in both periodontal disease and caries immunity. Regulatory T cell populations from gingival of periodontal disease patients or peripheral blood mononuclear cells of orally-immunized human subjects will be isolated and characterized for their phenotype (e.g., Leu 1, Leu 4, Leu 3a and Leu 2a) and for Fc receptor expression (e.g., Fc alpha R, Fc gamma R and Fc mu R). Furthermore, purified subsets of T cells will be cloned and hybridoma lines generated for analysis of isotype-specific helper and suppressor function in B cell proliferation, differentiation and Ig synthesis. Special attention will be given to lymphokine analysis including IL 2, IL 4 and Il 5, and especially isotype specific lymphokines (e.g., FcR and immunoglobulin binding factors). Isotype-specific lymphokines will be extensively characterized using modern molecular biology techniques. We will construct cDNA libraries with the gamma gtll system, by in vitro transcription and translation using the pSP64 system and by use of oligonucleotide probes for the analysis of isotype-specific regulatory T cell molecules. This grant proposal represents a comprehensive molecular and cellular analysis of isotype-specific regulatory T cells which are involved in both human periodontal disease and caries immunity.

令人信服的证据表明，免疫生物学相互作用对于疾病的发生和预防非常重要两大口腔疾病，即牙周病和牙病龋齿。例如，多克隆和抗原特异性免疫对牙周病原菌的反应，例如牙龈拟杆菌 (Bg) 和放线菌嗜血杆菌 (Ha) 发挥重要作用牙龈组织破坏发展中的作用牙周疾病。也有研究表明，口服人类注射变形链球菌疫苗可诱导粘膜中的抗原特异性分泌型 IgA (S-IgA) 反应相关分泌物，包括唾液、眼泪、初乳和粘液胃肠道和上呼吸道的分泌物，并且产生抗原特异性 IgA 的细胞出现在在这些外部 IgA 反应之前的外周循环分泌物可能是常见粘膜免疫的一部分系统。但人们对监管知之甚少机制，尤其是 T 细胞参与这些免疫回应。在这方面，本拨款提案的总体目标是研究 T 细胞调节的细胞和分子方面牙周病和龋齿的免疫反应免疫。来自牙龈的调节性T细胞群牙周病患者或外周血单核细胞口服免疫的人类受试者将被隔离并以其表型为特征（例如，Leu 1、Leu 4、Leu 3a 和 Leu 2a) 和 Fc 受体表达（例如 Fc α R、Fc γ R 和 Fc mu R)。此外，纯化的 T 细胞亚群将被克隆并产生杂交瘤系用于分析 B 细胞中同种型特异性辅助和抑制功能增殖、分化和 Ig 合成。特别关注将进行淋巴因子分析，包括 IL 2、IL 4 和 Il 5，尤其是同种型特异性淋巴因子（例如 FcR 和免疫球蛋白结合因子）。同种型特异性淋巴因子将使用现代分子生物学进行广泛的表征技术。我们将用gamma构建cDNA文库 gtll系统，通过体外转录和翻译使用 pSP64系统并使用寡核苷酸探针进行分析同种型特异性调节性 T 细胞分子。这笔补助金该提案代表了全面的分子和细胞相关同种型特异性调节性 T 细胞的分析在人类牙周病和龋齿免疫中。