Immunobiology & Transplant Science Center, Department of Surgery, Houston Methodist Hospital, Texas Medical Center, Houston, Texas, USA.
Curr Opin Organ Transplant. 2019 Dec;24(6):664-669. doi: 10.1097/MOT.0000000000000707.
Allograft rejection involves both innate and adaptive immune cells, and the adaptive immune cells have dominated transplant studies for decades. Recent studies have identified surprising new features for the innate immune cells, including memory recall responses, which may have significant implications in further improvement of transplant outcomes.
Transplant survival is excellent in the short-term, but the long-term graft outcomes are not so, and most grafts are continuously lost to chronic rejection in the clinic. In both animal models and clinical settings, graft loss to chronic rejection is often dominated by innate immune cells, especially macrophages and natural killer (NK) cells in the grafts. Recent studies suggest that innate immune cells can acquire features of adaptive cells in that they either directly sense allogeneic nonself or become 'trained' in the allogeneic milieu, where they show features of memory recall responses. In certain models, targeting the adaptive features of such innate immune cells can promote long-term allograft survival. These findings may open new therapeutic opportunities in promoting transplant survival in the clinic.
The discovery of donor specificity and memory recall responses of certain innate immune cells, which are prominently featured in chronic allograft rejection, may open novel therapeutic opportunities in transplantation, as well as in treatment of cancers and autoimmune diseases.
同种异体移植物排斥反应涉及固有免疫细胞和适应性免疫细胞，几十年来，适应性免疫细胞一直是移植研究的主导。最近的研究为固有免疫细胞确定了令人惊讶的新特征，包括记忆性应答，这可能对进一步改善移植结果具有重要意义。
短期内移植的存活率非常高，但长期移植物的结果并不理想，在临床上，大多数移植物因慢性排斥反应而不断丢失。在动物模型和临床环境中，慢性排斥反应导致的移植物丢失通常由固有免疫细胞主导，尤其是移植物中的巨噬细胞和自然杀伤（NK）细胞。最近的研究表明，固有免疫细胞可以获得适应性细胞的特征，即它们可以直接感知同种异体非自身，或者在同种异体环境中“训练”，从而表现出记忆性应答的特征。在某些模型中，针对此类固有免疫细胞的适应性特征进行靶向治疗可以促进长期同种异体移植物的存活。这些发现可能为促进临床移植中的移植物存活提供新的治疗机会。
在慢性同种异体移植物排斥反应中显著表现出的供体特异性和某些固有免疫细胞的记忆性应答的发现，可能为移植以及癌症和自身免疫性疾病的治疗开辟新的治疗机会。
