移植免疫學之新進展

Recent Advances in Transplant Immunology

移植免疫有別於一般的病原菌感染免疫反應，免疫系統所針對的目標主要為捐贈者與受贈者相異之人類白血球抗原（human leukocyte antigen, HLA）。而HLA為免疫系統中呈現抗原之重要蛋白質，也因此造成了移植免疫反應中，需考慮捐贈者和受贈者二套免疫系統的互動，包括移植造成特有之“直接”、“半直接”與“間接”呈現（direct，semi-direct and indirect presentation）。也因此，不同器官所含之免疫細胞數量不同，進入受贈者會造成“反直接”呈現（inverted direct allorecognition），由捐贈者T淋巴球活化受贈者B淋巴球，產生早期的排斥抗體。過去的被認為在排斥中較不重要之先天免疫系統，在近年之研究發現包括單核細胞（monocyte）、巨噬細胞（macrophage）及自然殺手細胞（natural killer cell），透過各自不同的機轉，皆可獨立於後天免疫系統之外造成排斥反應。而近幾年因探測工具進步而新興之細胞外囊泡（extracellular vesicle, EV）研究，可發現捐贈者之EV在半直接呈現中扮演重要角色，可活化受贈者淋巴球而引起快速之排斥反應。除了HLA做為主要排斥抗原外，許多其他的異體抗原亦可啟動免疫統成排斥。全面了解排斥反應之啟動機轉，有助於精進術前配對，病理診斷。另外，針對作用機轉，同時發展治療藥物，希望將來在現有的移植藥物基礎上，可以有比目前更好的排斥藥物組合，以延長移植器官之存活年限並改善病患之生活品質。

Immune response evoked by organ transplantation is different from common infectious pathogen in the aspect of antigen. The major alloantigen is human leukocyte antigen (HLA), a key protein for antigen presentation in adaptive immune responses. Hence, there is interactions between the two immune systems of donor and recipient respectively in the process of rejection. There are “indirect”, “direct” and “semidirect” presentations in alloimmune response and recently a phenomenon named “inverted direct” presentation was reported for transplant organs with abundant donor lymphocytes. For the innate immunity, there is new evidence that innate immune cells including monocyte, macrophage and natural killer cell could be activated by alloantigens. Besides, emerging researches on extracellular vesicles (EV) help to unveil cellular interaction in organ rejection thanks to advances in EV manipulation techniques. For alloantigen, several non-HLA proteins were proved to be allogenic and they should be put into consideration in pre-transplantation matching and post-transplantation monitoring. In conclusion, recent advances in transplant immunology showed several new issues, which are potential targets for pre-transplantation evaluation and post-transplantation management.