DENDRITIC CELLS & ACTINOBACILLUS ACTINOMYCETEMCOMITANS

树突状细胞

• 批准号: 6721202
• 负责人: PAUL J EZZO
• 金额: $ 12.14万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6721202
• 关键词: Actinobacillus actinomycetemcomitans; apoptosis; bacteria infection mechanism; bacterial toxins; biopsy; clinical research; confocal scanning microscopy; dendritic cells; dental disorder chemotherapy; dental disorder diagnosis; enzyme linked immunosorbent assay; gingiva; helper T lymphocyte; human subject; human therapy evaluation; immunofluorescence technique; immunoregulation; mixed tissue /cell culture; monoclonal antibody; morphometry; patient oriented research; periodontitis; phenotype; polymerase chain reaction; stainings

DESCRIPTION: Dr. Ezzo's long-term goal is to establish a successful career in academic dentistry. His immediate career goal is to further his development as an independent researcher in the area of clinically-oriented periodontal research. The research environment established at Baylor College of Dentistry (BCD) by Dr. Christopher Cutler, in collaboration with Dr. Jacques Banchereau at the Baylor Institute for Immunological Research (BIIR), will enable Dr. Ezzo to pursue his career development in a unique scientific/clinical niche. Furthermore, Dr. Martha Nunn, a biostatistician with expertise in designing and analyzing clinical trials, will co-mentor Dr. Ezzo. Dr. Cutler has established a collaboration with Dr. J. Banchereau as a result of common interests including: 1) identification and characterization of different dendritic cell (DC) subsets in human tissues, 2) impact of DCs on infectious disease, and 3) ability of DCs to induce protective immunity against infection. At BCD and BIIR, greater than 80 percent of Dr. Ezzo's time will be appropriated for the development of a research career. A systematic plan including courses in clinical research has been developed in order to broaden the knowledge Dr. Ezzo received in his Dentist/Scientist Award training. Both the didactic and research phases of the career plan will allow Dr. Ezzo to expand his experience in clinical research and to achieve his career goals. Characterizing the interaction between the DC and A. actinomycetemcomitans (Aa) is a logical "next step" in the process of career building for Dr. Ezzo. Dr. Ezzo's scientific background involves characterizing the T cell response to Aa and will be helpful in elucidating the importance of the DC in the immune response to this periodontal pathogen. DCs have been referred to as "nature's adjuvant" due to their ability to efficiently prime naive T cells. Their work has established that the periodontium is a significant repository of DC subsets. Their role in the immune response to periodontal pathogens, like Aa, is presently unknown. Distinct DC subsets, derived from myeloid and lymphoid precursors, are capable of providing different cytokine microenvironments that promote either Th1 or Th2 T cell development. The DC subset elicited during an infection with Aa, therefore, may have a profound effect on the outcome of infection. The hypothesis is that the predominant DC subset elicited in LJP lesions is differentially susceptible to Aa and its leukotoxin (lkt). Lkt preferentially targets myeloid cell derived-DCs that bear sensitivity to its effects. These subsets are eliminated, contributing to a pronounced Th1 bias. An inflammatory response ensues resulting in the inappropriate destruction of periodontal tissues. This hypothesis will be addressed by the following aims: 1) to characterize in situ the DC subsets found in gingiva from UP patients before and after clinical treatment, 2) to isolate and characterize DCs from UP patients, and 3) to perform in vitro studies of DC phenotype and function after co-culture with lkt+lkt-Aa.

描述：Ezzo博士的长期目标是建立一个成功的职业生涯， 学术牙科他近期的职业目标是进一步发展， 临床牙周领域的独立研究者， research.贝勒牙科学院建立的研究环境 (BCD)克里斯托弗·卡特勒博士与雅克·班什罗博士合作 贝勒免疫学研究所（BIIR）的研究，将使Ezzo博士 在一个独特的科学/临床利基追求他的职业发展。 此外，Martha纳恩博士是一位生物统计学家，擅长设计和 临床试验分析师将共同指导艾佐医生卡特勒博士已经证实 由于共同的兴趣，与J. Banchereau博士合作 包括：1）不同树突状细胞的鉴定和表征 (DC)人组织中的亚群，2）DC对感染性疾病的影响，和3） DC诱导抗感染保护性免疫的能力。在BCD和 BIIR，Ezzo博士80%以上的时间将用于 发展研究事业。一个系统的计划，包括课程 临床研究已经发展，以扩大知识博士Ezzo 在他的牙医/科学家奖培训中获得。无论是说教和 职业规划的研究阶段将使Ezzo博士能够扩展他的经验 从事临床研究并实现他的职业目标。表征 DC和A之间的相互作用。actinomycetemcomitans（Aa）是一个逻辑上的“下一个 在Ezzo博士的职业生涯建设过程中的一步”。Ezzo博士的科学 背景技术涉及表征T细胞对Aa的应答， 有助于阐明DC在免疫应答中的重要性， 牙周病原体DC被称为“天然佐剂”，这是由于 它们有效地引发初始T细胞的能力。他们的工作建立了 牙周组织是DC亚群的重要储存库。农村妇女在消除 对牙周病原体如Aa的免疫应答目前是未知的。 来自骨髓和淋巴前体的不同DC亚群能够 提供不同的细胞因子微环境， Th 2 T细胞发育。DC亚群在Aa感染期间引起， 因此，可能会对感染的结果产生深远的影响。的 假设LJP病变中引起的主要DC亚群是 对Aa及其白细胞毒素（lkt）的敏感性差异。Lkt优先 靶向骨髓细胞衍生的DC，其对其作用敏感。这些 亚群被消除，导致明显的Th 1偏倚。炎性 反应过度导致牙周组织的不适当破坏 组织中这一假设将通过以下目标来解决：1） 原位表征之前在UP患者牙龈中发现的DC亚群 临床治疗后，2）从UP中分离和鉴定DC 患者，和3）进行DC表型和功能的体外研究， 与lkt+lkt-Aa共培养。