Department of Surgery, Transplant Unit & Wellman Photomedicine Center Massachusetts General Hospital & Harvard Medical School, Boston, MA, USA.
Immunotherapy. 2011 Jun;3(6):757-70. doi: 10.2217/imt.11.2.
The transplantation of allogeneic skin grafts is associated with a potent inflammatory immune response leading to the destruction of donor cells and the rejection of the graft. Shortly after transplantation, skin dendritic cells (DCs) migrate out of the graft through lymphatic vessels and infiltrate the recipient's draining lymph nodes where they present donor antigens via two mechanisms: the direct pathway, in which T cells recognize intact donor MHC antigens on donor DCs; and the indirect pathway, involving T-cell recognition of donor peptides bound to self-MHC molecules on recipient DCs. Some recent studies have suggested that T cells can become activated via recognition of donor MHC molecules transferred on recipient antigen-presenting cells (semidirect pathway). Activation of T cells via direct or indirect allorecognition is sufficient to trigger acute rejection of allogeneic skin grafts. In addition, allospecific antibodies contribute to the rejection process either by killing allogeneic targets in a complement-dependent fashion or by opsonizing donor cells and forming immune complexes. Finally, several studies demonstrate that NK cells, activated due to missing self-MHC class I molecules on allogeneic cells, are involved in allogeneic skin graft rejection via direct killing of donor cells and through the production of proinflammatory cytokines including IFN-γ and TNF-α.
同种异体皮肤移植物的移植会引起强烈的炎症免疫反应，导致供体细胞的破坏和移植物的排斥。移植后不久，皮肤树突状细胞（DCs）通过淋巴管移出移植物，并浸润受者引流淋巴结，通过两种机制提呈供体抗原：直接途径，其中 T 细胞识别供体 DC 上完整的供体 MHC 抗原；间接途径，涉及 T 细胞识别受者 DC 上与自身 MHC 分子结合的供体肽。一些最近的研究表明，T 细胞可以通过识别转移到受者抗原呈递细胞上的供体 MHC 分子而被激活（半直接途径）。通过直接或间接同种异体识别激活 T 细胞足以触发同种异体皮肤移植物的急性排斥。此外，同种异体抗体通过补体依赖性方式杀伤同种异体靶标或通过调理供体细胞并形成免疫复合物，有助于排斥过程。最后，几项研究表明，由于同种异体细胞上缺失自身 MHC I 类分子，NK 细胞被激活，通过直接杀伤供体细胞以及产生包括 IFN-γ和 TNF-α在内的促炎细胞因子参与同种异体皮肤移植物排斥。
