MRC Centre for Transplantation, King's College London School of Medicine at Guy's, King's and St. Thomas' Hospitals, London, UK.
Eur J Immunol. 2011 Jan;41(1):89-96. doi: 10.1002/eji.201040759. Epub 2010 Nov 11.
Tertiary lymphoid organs can form at sites of chronic inflammation. Their presence has been mainly associated with tissue destruction. In transplantation, there is a dynamic immune response as in chronic inflammation. Indeed, the presence of tertiary lymphoid organs has been associated with chronic rejection. In addition to a destructive alloimmune response, secondary lymphoid organs are also important in transplant tolerance. We hypothesised that tertiary lymphoid organs may also form during transplantation tolerance as this process also requires an active local immune response. If so, their presence may enhance tolerance, resulting in better graft function rather than chronic rejection. Using a mouse kidney allograft model of tolerance, we demonstrate the formation of tertiary lymphoid organs within tolerated allografts. Tertiary lymphoid organs are supplied by high endothelial venules, and contain T and B cells, macrophages, DC, Foxp3(+) T cells, donor MHC class II(+) cells and recipient cells presenting donor-derived allopeptides. Formation of tertiary lymphoid organs and the presence of immune cells within them are associated with superior graft function, suggesting that tertiary lymphoid organs act to amplify the prevailing immune response, be it a tolerant and beneficial immune response or the previously described destructive alloimmunity.
三级淋巴器官可在慢性炎症部位形成。它们的存在主要与组织破坏有关。在移植中，会像慢性炎症一样发生动态免疫反应。事实上，三级淋巴器官的存在与慢性排斥反应有关。除了破坏性的同种异体免疫反应外，次级淋巴器官在移植耐受中也很重要。我们假设，在移植耐受过程中也可能形成三级淋巴器官，因为这一过程也需要活跃的局部免疫反应。如果是这样，它们的存在可能会增强耐受性，从而改善移植物功能，而不是慢性排斥反应。使用耐受的小鼠肾脏同种异体移植模型，我们证明了三级淋巴器官在耐受的同种异体移植物内的形成。三级淋巴器官由高内皮静脉提供，并包含 T 和 B 细胞、巨噬细胞、DC、Foxp3(+)T 细胞、表达供体 MHC Ⅱ类分子的细胞和呈现供体来源同种肽的受体细胞。三级淋巴器官的形成和其中免疫细胞的存在与移植物功能的改善相关，这表明三级淋巴器官可以放大当前的免疫反应，无论是耐受和有益的免疫反应，还是之前描述的破坏性同种异体免疫反应。
