DENDRITIC CELLS FOR INDUCTION OF ALLOGRAFT TOLERANCE

描述（改编自申请人的摘要）：本提案旨在 开发使用树突状细胞（DC）诱导同种异体耐受的新方法， 小鼠模型该建议是基于静脉输注胸腺 与对照组相比， 脾DC显示受损的胸腺归巢能力，并且没有 诱导耐受性的能力。这些数据得到了以下能力的证实： 胸腺DC在过继转移后选择性地归巢于胸腺， 宽容本提案的总体目标是：1）了解 由同种异体DC诱导的耐受的机制，2）定义DC 具有最高致耐受性能力的亚群，和3）开发 旨在最佳利用收养性转移的技术方法 DC诱导同种异体耐受。该提案的重点是进一步发展 这些方法将使DC耐受原疗法在临床上可行。在 特别是，他们建议充分描绘这种影响的机制， 用于鉴定和分离具有治疗作用DC的改进方法 潜力，增加耐受性的持续时间，探索必要的表型 独特的胸腺归巢，并开发体外技术，以繁殖或 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具有重要的临床应用， 与其他胸腺内给药方法相比， 引入新抗原以防止同种异体移植物排斥和其它 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.