DENDRITIC CELLS FOR INDUCTION OF ALLOGRAFT TOLERANCE

描述(改编自申请人的摘要)：本提案旨在 目的：开发用树突状细胞(DC)诱导同种异体耐受的新方法。 老鼠模型。这项提议是基于观察到的，即IV.注入的胸腺 树突状细胞选择性结合胸腺和诱导同种异体抗原耐受的比较 表现出胸腺归巢功能受损的脾DC 诱导耐受性的能力。这些数据被以下能力所证实 胸腺树突状细胞在收养转移后选择性地回到胸腺内导致 宽容。这项建议的总体目标是1)了解 同种异体DC诱导耐受的机制(S)2)DC的定义 具有最高耐受能力的亚群，以及3)发展 旨在优化采用技术转让的技术方法 DC诱导同种异体耐受。这项建议的重点是进一步发展 使DC耐受原疗法在临床上可行的方法学。在……里面 特别是，他们建议充分描述这方面的影响机制。 系统，改进DC的鉴定和分离方法 潜力，增加耐受的持续时间，探索必要的表型 用于独特的胸腺归巢，并开发体外技术来繁殖或 使这些细胞永生。除了基本的含义外，他们还提出 他们的发现最终可能会有重大的临床应用， 与其他方法相比，胸腺内注射具有相当大的实用优势 引入新抗原以避免同种异体移植排斥反应和其他 T细胞介导的疾病过程。

DESCRIPTION (Adapted from the Applicant's Abstract): This proposal is designed to develop new methods using dendritic cells (DC) to induce allotolerance in a mouse model. The proposal is based on the observation that i.v. infused thymic DCs selectively home to thymus and induce alloantigenic tolerance as compared to splenic DCs that show impaired thymic homing capabilities and do not have the ability to induced tolerance. These data are corroborated by the ability of thymic DCs to selectively home in the thymus after adoptive transfer leading to tolerance. The overall goals of this proposal are to 1) understand the mechanism(s) of the tolerance induced by allogeneic DCs, 2) define the DC subpopulation with the highest tolerogenic capability, and 3) develop the technical methodologies designed to optimize the use of adoptive transfer of DCs to induce allotolerance. The focus of this proposal is to further develop methodologies that will render DC tolerogen therapies clinically feasible. In particular, they propose to fully delineate mechanisms of effects in this system, improve methods for identification and isolation of DC with therapeutic potential, increase the duration of tolerance, explore the phenotypes necessary for unique thymic homing, and develop in vitro techniques to propagate or immortalize these cells. In addition to basic implications, they propose that their findings may ultimately have significant clinical applications, with considerable practical advantages over other methods for intrathymic introduction of neo-antigens to obviate allograft rejection and other T-cell-mediated disease processes.