The Migration of Peripheral Macrophages to TNCs and Their Role in Antigen Presentation
外周巨噬细胞向 TNC 的迁移及其在抗原呈递中的作用
基本信息
- 批准号:0412822
- 负责人:
- 金额:$ 42万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-09-01 至 2007-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Project Abstract: The migration of peripheral macrophages to thymic nurse cells and their role in antigen presentation.T cells ultimately function to remove virally infected cells from the body. In order for them to accomplish this task, T cells have to be able to distinguish cells that are a part of the body, called self-cells, from agents that are foreign to the body. During development in the thymus, self antigens are presented to developing T cells. The T cells through their antigen receptor (TcR) have the ability to recognize antigens on the surfaces of the antigen presenting (APC) thymic cells. When a self-antigen is presented to developing T cells, its TcR binds tightly to this protein on the surface of an APC and that T cell is induced to die through a process called apoptosis. This makes sense because if the T cell was allowed to mature and released in the blood stem, it would recognize that antigen and kill the normal B cell to which it was attached. Mature T cells are able to determine which self-cells are infected with viruses and which produce foreign proteins on the cell surface. This is most important when one realizes that viruses live and hide inside of the cells that they infect. The Guyden lab has developed cell lines from one of the APCs that function during this process and are called thymic nurse cells (TNCs). These cells are unique to the body because they actually take up developing thymocytes into their cytoplasm during antigen presentation. A major question yet to be answered is, how does all of the large number of self antigens get to the thymus for antigen presentation, when most self antigens reside outside of the thymus? Preliminary results show that other antigen presenting cells like macrophages and dendritic cells exist within this TNC complex along with developing thymocytes. Further, the macrophages that are stained and returned to the gut of a mouse can migrate to the thymus and into TNCs. It is proposed that macrophages and dendritic cells, which have a primary function of removing dead and apoptotic cells from the body, have the ability to present self antigens resulting from dead cells to developing T cells within the TNC complex. Studies using genetically manipulated animals that have T cells with only one TcR will be carried out. Migration of macrophages or dendritic cells transferred into the gut of these animals will be followed and their ability to induce apoptosis in developing T cells in large enough numbers will be determined statistically. An antibody to TNCs has also been developed and will be used to treat normal mice, which will result in the elimination of their TNCs. The population of T cells that mature from these treated animals will be analyzed. If TNCs function during antigen presentation and self-antigen cannot be presented in their absence, mature T cell that have the ability to attack self cells or are auto-immunogenic will be detected. Broader Impact: Minority students will be trained and will be involved in this project. Funds coming from this project will allow the training of seven PhD students. Over the years of NSF funding, 38 minority undergraduate students have participated in research in the laboratory and have since obtained their PhD or MD degrees or are continuing students. Currently, there are: 1 PhD, 2 Masters, and 3 undergraduate students.
项目摘要:外周巨噬细胞向胸腺哺育细胞的迁移及其在抗原提呈中的作用。T细胞最终起到清除体内病毒感染细胞的作用。为了完成这项任务,T细胞必须能够区分属于身体一部分的细胞,称为自我细胞,与身体外部的介质。在胸腺发育过程中,自身抗原被提呈给发育中的T细胞。T细胞通过其抗原受体(TCR)识别抗原提呈(APC)胸腺细胞表面的抗原。当一种自身抗原被提供给发育中的T细胞时,它的TCR与APC表面的这种蛋白质紧密结合,该T细胞通过一个称为凋亡的过程被诱导死亡。这是有道理的,因为如果T细胞被允许成熟并在血液干细胞中释放,它就会识别这种抗原,并杀死它附着的正常B细胞。成熟的T细胞能够确定哪些自身细胞感染了病毒,哪些细胞表面产生了外源蛋白。当人们意识到病毒生活和隐藏在它们感染的细胞内时,这一点是最重要的。盖登实验室已经从其中一种在这一过程中发挥作用的APC开发出细胞系,称为胸腺哺育细胞(TNCs)。这些细胞对人体来说是独一无二的,因为它们实际上在抗原呈递期间负责将胸腺细胞发育成细胞质。一个尚未回答的主要问题是,当大多数自身抗原驻留在胸腺外时,大量的自身抗原是如何到达胸腺进行抗原呈递的?初步结果表明,随着胸腺细胞的发育,TNC复合体中还存在其他抗原提呈细胞,如巨噬细胞和树突状细胞。此外,被染色并返回到小鼠肠道的巨噬细胞可以迁移到胸腺和肿瘤细胞。巨噬细胞和树突状细胞具有清除体内死亡和凋亡细胞的主要功能,它们具有将死亡细胞产生的自身抗原呈递给TNC复合体内发育中的T细胞的能力。将使用T细胞只有一个TCR的转基因动物进行研究。将跟踪巨噬细胞或树突状细胞转移到这些动物的肠道中,并从统计学上确定它们在足够数量的发育中的T细胞诱导凋亡的能力。还开发了一种针对跨国公司的抗体,并将用于治疗正常小鼠,这将导致消除它们的跨国公司。将分析从这些处理过的动物中成熟的T细胞的数量。如果TNCs在抗原提呈过程中发挥作用,并且自身抗原不能提呈,则可以检测到具有攻击自身细胞能力或自身免疫原性的成熟T细胞。更广泛的影响:少数民族学生将接受培训,并将参与到这个项目中来。来自该项目的资金将用于培训7名博士生。在NSF资助的这些年里,38名少数族裔本科生参与了实验室的研究,并从那以后获得了博士或医学博士学位,或者是继续学习的学生。目前有:博士1人,硕士2人,本科生3人。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jerry Guyden其他文献
Jerry Guyden的其他文献
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{{ truncateString('Jerry Guyden', 18)}}的其他基金
The Relationship Between Thymic Nurse Cells and Macrophages During MHC Restriction
MHC限制期间胸腺护理细胞与巨噬细胞的关系
- 批准号:
0108778 - 财政年份:2001
- 资助金额:
$ 42万 - 项目类别:
Continuing Grant
Thymic Nurse Cells: Internalization, Survival or Death of Thymocytes
胸腺护理细胞:胸腺细胞的内化、存活或死亡
- 批准号:
9807242 - 财政年份:1998
- 资助金额:
$ 42万 - 项目类别:
Continuing grant
Molecular Approach to the Study of Thymic Nurse Cell Function
研究胸腺护理细胞功能的分子方法
- 批准号:
9602001 - 财政年份:1996
- 资助金额:
$ 42万 - 项目类别:
Standard Grant
A Study of Thymic Nurse Cell Function
胸腺护理细胞功能的研究
- 批准号:
9218859 - 财政年份:1993
- 资助金额:
$ 42万 - 项目类别:
Continuing grant
T-Cell Development: Studies In Vivo and in Organ Culture
T 细胞发育:体内和器官培养研究
- 批准号:
8714987 - 财政年份:1988
- 资助金额:
$ 42万 - 项目类别:
Continuing grant
Neuromodulation by Histamine and Serotonin in Hippocampus
海马体中组胺和血清素的神经调节
- 批准号:
8606419 - 财政年份:1986
- 资助金额:
$ 42万 - 项目类别:
Continuing grant
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