Department of Surgery, Washington University in St. Louis, St. Louis, MO, USA.
Department of Surgery, Northwestern University, Chicago, IL, USA.
Am J Transplant. 2018 Jan;18(1):216-225. doi: 10.1111/ajt.14437. Epub 2017 Aug 23.
Immunological requirements for rejection and tolerance induction differ between various organs. While memory CD8 T cells are considered a barrier to immunosuppression-mediated acceptance of most tissues and organs, tolerance induction after lung transplantation is critically dependent on central memory CD8 T lymphocytes. Here we demonstrate that costimulation blockade-mediated tolerance after lung transplantation is dependent on programmed cell death 1 (PD-1) expression on CD8 T cells. In the absence of PD-1 expression, CD8 T cells form prolonged interactions with graft-infiltrating CD11c cells; their differentiation is skewed towards an effector memory phenotype and grafts are rejected acutely. These findings extend the notion that requirements for tolerance induction after lung transplantation differ from other organs. Thus, immunosuppressive strategies for lung transplant recipients need to be tailored based on the unique immunological properties of this organ.
免疫排斥和耐受诱导的免疫学要求在不同器官之间存在差异。虽然记忆 CD8 T 细胞被认为是大多数组织和器官免疫抑制介导接受的障碍，但肺移植后的耐受诱导则严重依赖于中央记忆 CD8 T 淋巴细胞。在这里，我们证明了肺移植后通过共刺激阻断介导的耐受依赖于 CD8 T 细胞上的程序性细胞死亡 1（PD-1）表达。在缺乏 PD-1 表达的情况下，CD8 T 细胞与移植物浸润的 CD11c 细胞形成延长的相互作用；它们的分化偏向于效应记忆表型，移植物被急性排斥。这些发现扩展了这样一种观念，即肺移植后诱导耐受的要求与其他器官不同。因此，肺移植受者的免疫抑制策略需要根据该器官的独特免疫学特性进行调整。
