T CELL REGULATION OF CARIES IMMUNITY/PERIODONTAL DISEASE

令人信服的证据表明，免疫生物学 相互作用在发展和预防 两种主要的口腔疾病，即，牙周病与牙科 龋齿 例如，多克隆和抗原特异性免疫 对牙周病的反应，例如，牙龈拟杆菌（Bg） 放线菌伴嗜血杆菌（Haemophilis actinomycetemcomitans，Ha）在其中起重要作用 在牙龈组织破坏发展中的作用， 牙周病 研究还表明，口服 向人施用变形链球菌疫苗诱导 粘膜中抗原特异性分泌型伊加（S-IgA）反应 相关分泌物，包括唾液、泪液、初乳和粘液 胃肠道和上呼吸道的分泌物， 并且抗原特异性伊加产生细胞出现在 外周循环之前，伊加反应，在这些外部 分泌物可能是常见的粘膜免疫的一部分， 系统 然而，对监管知之甚少。 机制，特别是T细胞参与这些免疫 应答 在这方面，本赠款提案的总体目标是 研究T细胞调节的细胞和分子方面， 牙周病和龋病免疫反应 免疫力 来自牙龈的调节性T细胞群 牙周病患者或外周血单个核细胞 的口服免疫的人类受试者将被分离， 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 μ 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。 特别注意 进行IL 2、IL 4、IL 5等淋巴因子检测， 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 会用现代分子生物学进行广泛的表征 技术. 我们将用γ-淀粉酶构建cDNA文库， gtll系统，通过体外转录和翻译，使用 pSP 64系统并通过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。 这笔赠款 该提案代表了一个全面的分子和细胞 分析涉及的同种型特异性调节性T细胞 在人类牙周病和龋齿免疫中。

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.