Borges Thiago J, Lang Benjamin J, Lopes Rafael L, Bonorino Cristina
Faculdade de Biociências e Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul , Porto Alegre, Rio Grande do Sul , Brazil.
Department of Radiation Oncology, Center for Life Sciences, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA , USA.
Front Immunol. 2016 Aug 9;7:303. doi: 10.3389/fimmu.2016.00303. eCollection 2016.
The immunological mechanisms that evolved for host defense against pathogens and injury are also responsible for transplant rejection. Host rejection of foreign tissue was originally thought to be mediated mainly by T cell recognition of foreign MHC alleles. Management of solid organ transplant rejection has thus focused mainly on inhibition of T cell function and matching MHC alleles between donor and host. Recently, however, it has been demonstrated that the magnitude of the initial innate immune responses upon transplantation has a decisive impact on rejection. The exact mechanisms underlying this phenomenon have yet to be characterized. Ischemic cell death and inflammation that occur upon transplantation are synonymous with extracellular release of various heat shock proteins (Hsps), many of which have been shown to have immune-modulatory properties. Here, we review the impact of Hsps upon alloimmunity and discuss the potential use of Hsps as accessory agents to improve solid organ transplant outcomes.
为抵御病原体和损伤而进化出的免疫机制同样也导致了移植排斥反应。宿主对外来组织的排斥最初被认为主要是由T细胞识别外来MHC等位基因介导的。因此,实体器官移植排斥反应的管理主要集中在抑制T细胞功能以及供体和宿主之间MHC等位基因的匹配上。然而,最近有研究表明,移植时初始固有免疫反应的强度对排斥反应具有决定性影响。这一现象背后的确切机制尚未明确。移植时发生的缺血性细胞死亡和炎症与各种热休克蛋白(Hsps)的细胞外释放同义,其中许多热休克蛋白已被证明具有免疫调节特性。在此,我们综述热休克蛋白对同种免疫的影响,并讨论热休克蛋白作为辅助剂改善实体器官移植结果的潜在用途。