Tertiary lymphoid organs in renal allografts can be associated with donor-specific tolerance rather than rejection
Tertiary lymphoid organs in renal allografts can be associated with donor-specific tolerance rather than rejection
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DOI：
10.1002/eji.201040759
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发表时间：
2011-01-01
影响因子：
5.4
通讯作者：
Wong, Wilson
中科院分区：
文献类型：
--
作者：
Brown, Kathryn;Sacks, Steven H.;Wong, Wilson
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，存在与慢性炎症中一样的动态免疫应答。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。我们假设三级淋巴器官也可能在移植耐受过程中形成，因为这一过程也需要积极的局部免疫应答。如果是这样，它们的存在可能会增强耐受性，导致更好的移植功能，而不是慢性排斥。使用小鼠肾移植耐受模型，我们证明了三级淋巴器官的形成耐受同种异体移植。三级淋巴器官由高内皮小静脉供应，并含有T和B细胞、巨噬细胞、DC、Foxp3（+）T细胞、供体MHC II类+细胞和呈递供体衍生的同种异体肽的受体细胞。三级淋巴器官的形成和其中免疫细胞的存在与上级移植物功能相关，表明三级淋巴器官起到放大主要免疫应答的作用，无论是耐受性和有益的免疫应答还是先前描述的破坏性同种异体免疫。
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.