Gandy K L
Department of Experimental Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Immunol Res. 2000;22(2-3):147-64. doi: 10.1385/IR:22:2-3:147.
Tolerance of transplanted tissue has been a focus of immunologists for decades. Indeed, to some the birth of immunology and the search for tolerance of the non-self are synonymous. One of the most powerful and reproducible methods of tolerance induction to allogeneic tissue has involved infusion of donor-specific hematopoietic cells. Under certain conditions, such infusion can result in hematopoietic reconstitution that can be experimentally accomplished at a variety of different time-points in the life of an organism from the in utero period through adulthood, reconstitution at each time-point involving consideration of a different set of immunological and physiological parameters. When high levels of donor-derived hematopoietic reconstitution are achieved, tolerance induction to donor-specific antigens is reproducible and long-lasting. Unfortunately, however, clinical efforts to achieve such high levels of hematopoietic reconstitution have historically been unsuccessful or fraught with complications. Transplantation efforts have been plagued by failure of engraftment, graft-vs-host disease (GVHD), or severe immunoincompetence of the recipient. Laboratory and clinical efforts during the last decade have resulted in a variety of developments that may overcome these barriers: (1) methods have been devised in which cells that cause GVHD can be depleted from the hematopoietic graft while hematopoietic reconstitution potential is preserved, (2) methods of harvesting large numbers of cells with multilineage reconstitution potential have been devised (an accomplishment that seems to allow the immunological barrier to be overwhelmed), and (3) capitalizing on the above two principles, minimally toxic preconditioning regimens have been designed that allow allogeneic engraftment. This review will focus on some of the experimental and clinical data of the past and the experimental and clinical issues that loom ahead.
几十年来，移植组织的耐受性一直是免疫学家关注的焦点。事实上，对一些人来说，免疫学的诞生与寻找对非自身的耐受性是同义词。诱导对同种异体组织耐受性的最有效且可重复的方法之一是输注供体特异性造血细胞。在某些条件下，这种输注可导致造血重建，从子宫内期到成年期的生物体生命中的各种不同时间点都能通过实验实现造血重建，每个时间点的重建都涉及考虑不同的一组免疫和生理参数。当实现高水平的供体来源造血重建时，对供体特异性抗原的耐受性诱导是可重复且持久的。然而，不幸的是，历史上实现如此高水平造血重建的临床努力一直未成功或充满并发症。移植努力一直受到植入失败、移植物抗宿主病（GVHD）或受体严重免疫无能的困扰。过去十年的实验室和临床努力带来了各种可能克服这些障碍的进展：（1）已经设计出方法，可在保留造血重建潜力的同时从造血移植物中清除引起GVHD的细胞；（2）已经设计出收获大量具有多谱系重建潜力细胞的方法（这一成果似乎使免疫屏障被突破）；（3）利用上述两个原则，设计出了毒性最小的预处理方案，以实现同种异体植入。本综述将聚焦过去的一些实验和临床数据以及未来即将出现的实验和临床问题。
