Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA; email:
Department of Internal Medicine, Division of Hematology-Oncology, and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Annu Rev Pathol. 2018 Jan 24;13:219-245. doi: 10.1146/annurev-pathol-020117-043720. Epub 2017 Nov 3.
Allogeneic transplantation of foreign organs or tissues has lifesaving potential, but can lead to serious complications. After solid organ transplantation, immune-mediated rejection mandates the use of prolonged global immunosuppression and limits the life span of transplanted allografts. After bone marrow transplantation, donor-derived immune cells can trigger life-threatening graft-versus-host disease. T cells are central mediators of alloimmune complications and the target of most existing therapeutic interventions. We review recent progress in identifying multiple cell types in addition to T cells and new molecular pathways that regulate pathogenic alloreactivity. Key discoveries include the cellular subsets that function as potential sources of alloantigens, the cross talk of innate lymphoid cells with damaged epithelia and with the recipient microbiome, the impact of the alarmin interleukin-33 on alloreactivity, and the role of Notch ligands expressed by fibroblastic stromal cells in alloimmunity. While refining our understanding of transplantation immunobiology, these findings identify new therapeutic targets and new areas of investigation.
同种异体移植外来器官或组织具有救生潜力，但可导致严重并发症。在实体器官移植后，免疫介导的排斥反应需要长期的全身性免疫抑制，限制了移植同种异体移植物的寿命。骨髓移植后，供体来源的免疫细胞可引发危及生命的移植物抗宿主病。T 细胞是同种免疫并发症的主要介质，也是大多数现有治疗干预措施的靶点。我们回顾了除 T 细胞以外的多种细胞类型和调节致病性同种反应性的新分子途径的最新研究进展。关键发现包括作为潜在同种抗原来源的细胞亚群、先天淋巴细胞与受损上皮细胞以及与受者微生物组之间的串扰、警报素白细胞介素-33 对同种反应性的影响以及成纤维细胞基质细胞表达的 Notch 配体在同种免疫中的作用。在深化我们对移植免疫生物学的理解的同时，这些发现确定了新的治疗靶点和新的研究领域。
