T CELL REGULATION OF CARIES IMMUNITY/PERIODONTAL DISEASE

T 细胞对龋齿免疫/牙周病的调节

• 批准号: 3072191
• 负责人: HIROSHI KIYONO
• 金额: $ 5.44万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/3072191
• 关键词: Actinobacillus; B lymphocyte; Bacteroides gingivalis; Streptococcus mutans; T lymphocyte; cell differentiation; cellular immunity; clone cells; colostrums; dental caries; gastrointestinal system; gene expression; genetic transcription; genetic translation; gingiva; helper T lymphocyte; human tissue; humoral immunity; hybridomas; immunogenetics; immunoglobulin A; laboratory mouse; laboratory rat; leukocyte activation /transformation; microorganism genetics; microorganism immunology; molecular biology; oligonucleotides; oral bacteria; periodontium disorder; respiratory system; saliva; suppressor T lymphocyte; tear

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.

有令人信服的证据表明，免疫生物学 相互作用在疾病的发展和预防中非常重要 两大口腔疾病，即牙周病和牙科 龋齿。例如，多克隆和抗原特异性免疫 对牙周病原体的反应，如牙龈类杆菌(BG) 和伴放线嗜血杆菌(Ha)起重要作用 牙周组织破坏在牙周炎发生发展中的作用 牙周病。也有研究表明，口述 变形链球菌疫苗对人诱导物的免疫接种 粘膜中抗原特异性分泌型免疫球蛋白A(S-IgA)的反应 相关分泌物，包括唾液、泪水、初乳和粘液 胃肠道和上呼吸道的分泌物， 抗原特异性免疫球蛋白A产生细胞出现在 这些外周血中IgA反应之前的外周循环 分泌物可能是普通粘膜免疫的一部分 系统。然而，人们对监管机构知之甚少。 机制，特别是T细胞参与这些免疫 回应。在这方面，这项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 牙周病和龋病的免疫反应 豁免权。牙周组织中调节性T细胞亚群的研究 牙周病患者或外周血单核细胞 所有口服免疫的人类受试者将被隔离并 具有其表型的特征(例如，Leu1、Leu4、Leu3a和 Leu 2a)和Fc受体表达(例如，FcαR、Fc Gamma R和FC Mu R)。此外，纯化的T细胞亚群 将克隆并产生杂交瘤株用于分析 B细胞中同型特异性的辅助和抑制功能 增殖、分化和Ig合成。特别关注 将给予淋巴因子分析，包括IL-2，IL-4和IL-5， 尤其是同型特异性淋巴因子(例如，FCR和 免疫球蛋白结合因子)。同型特异性淋巴因子 将利用现代分子生物学进行广泛的表征 技巧。我们将用伽马基因构建cDNA库 GTLL系统，通过体外转录和翻译 PSP64系统并利用寡核苷酸探针进行分析 同型特异性调节性T细胞分子。这笔赠款 该提案代表了一种全面的分子和细胞 涉及的同型特异性调节性T细胞的分析 在人类牙周病和龋齿免疫中都是如此。