Ichim Thomas E, Zhong Robert, Min Wei-Ping
Department of Surgery, University of Western Ontario, London, Ont., Canada.
Transpl Immunol. 2003 Jul-Sep;11(3-4):295-306. doi: 10.1016/S0966-3274(03)00048-0.
Achieving immunological tolerance in transplantation has been a long sought-after goal since the 1960s. It is, therefore, interesting that the dendritic cells (DC), which are classically known as the most potent stimulators of T cell activation, are now also considered putative tools for tolerance induction. In line with this, much work has been performed using DC for vaccination and immune stimulation. Recently, great interest has been generated regarding the ability of DC to act as immune regulatory cells. Specific subsets of DC or immature DC (iDC) appear to be responsible for maintaining self-tolerance. In this review we will highlight our efforts at elucidating the contribution of DC in transplant tolerant in mice. Specifically, four strategies will be outlined that are currently being used for the generation of DC that have tolerogenic properties in the prevention of allograft rejection. The present study demonstrates that modulated iDC with blunted T cell stimulatory or antigen presentation abilities can afford transplant tolerance by minimizing T cell activation and proinflammatory cytokine production. Moreover, in an alternate strategy, normally matured DC have also been modulated such that alloreactive T cells are specifically targeted for deletion.
自20世纪60年代以来，在移植中实现免疫耐受一直是人们长期追求的目标。因此，有趣的是，树突状细胞（DC）传统上被认为是T细胞激活的最有力刺激物，现在也被视为诱导耐受的潜在工具。与此一致的是，已经开展了许多使用DC进行疫苗接种和免疫刺激的工作。最近，人们对DC作为免疫调节细胞的能力产生了极大兴趣。DC的特定亚群或未成熟DC（iDC）似乎负责维持自身耐受。在这篇综述中，我们将重点介绍我们在阐明DC对小鼠移植耐受的贡献方面所做的努力。具体而言，将概述目前用于生成具有致耐受性特性的DC以预防同种异体移植排斥的四种策略。本研究表明，具有减弱的T细胞刺激或抗原呈递能力的经调节的iDC可以通过最小化T细胞激活和促炎细胞因子产生来实现移植耐受。此外，在另一种策略中，正常成熟的DC也经过调节，使得同种异体反应性T细胞被特异性靶向清除。
