DENDRITIC CELLS & ACTINOBACILLUS ACTINOMYCETEMCOMITANS

树突状细胞

• 批准号: 6228863
• 负责人: PAUL J EZZO
• 金额: $ 11.35万
• 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 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6228863
• 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：伊佐博士的长期目标是在中国建立一个成功的职业生涯 学院派牙医。他的直接职业目标是进一步发展，成为 临床牙周领域的独立研究人员 研究。在贝勒口腔医学院建立的研究环境 (BCD)克里斯托弗·卡特勒博士与雅克·班切罗博士合作 在贝勒免疫研究所(BIIR)，将使Ezzo博士 在独特的科学/临床领域追求自己的事业发展。 此外，玛莎·纳恩博士，一位在设计和开发方面具有专业知识的生物统计学家 分析临床试验，将共同指导Ezzo博士。卡特勒博士已经建立了 出于共同利益与J.Banchereau博士的合作 包括：1)不同树突状细胞的鉴定和特性 (DC)人体组织中的亚群，2)DC对传染病的影响，以及3) 树突状细胞诱导抗感染保护性免疫的能力。在BCD和 BIIR，Ezzo博士80%以上的时间将分配给 研究事业的发展。包括课程在内的系统计划 临床研究的发展是为了拓宽Ezzo博士的知识 在他的牙医/科学家奖培训中获得。无论是说教还是说教 职业生涯规划的研究阶段将使Ezzo博士能够扩大他的经验 在临床研究和实现他的职业目标。描述了 放线菌伴生菌(AA)与DC之间的相互作用是合乎逻辑的下一步 在Ezzo博士的职业发展过程中迈出一步。Ezzo博士的科学 背景包括描述T细胞对AA的反应，并将 有助于阐明树突状细胞在免疫应答中的重要性 牙周病原体。由于以下原因，DCs一直被称为“大自然的佐剂” 它们高效地激发幼稚T细胞的能力。他们的工作已经确立了 牙周组织是DC亚群的重要储存库。他们在其中扮演的角色 对牙周病原体的免疫反应，如再生障碍性贫血，目前尚不清楚。 来自髓系和淋巴系前体的不同DC亚群能够 提供不同的细胞因子微环境，促进Th1或Th1 Th2T细胞发育。在感染再生障碍性贫血期间诱发的DC亚集， 因此，可能对感染的结局有深远的影响。这个 假设在LJP皮损中诱发的主要DC亚群是 对AA及其白毒素(LKT)有不同程度的易感性。LKT优先 以髓系细胞来源的DC为靶点，这些DC对其作用敏感。这些 子集被消除，导致明显的Th1偏向。一种煽动性的 随之而来的反应导致牙周的不适当破坏 纸巾。这一假设将通过以下目标加以解决：1) 就地鉴定UP患者牙周组织中发现的DC亚群 临床治疗后，2)从UP中分离和鉴定DC 患者，以及3)进行DC表型和功能的体外研究 与LKT+LKT-AA共培养。