Velardi Andrea, Ruggeri Loredana, Mancusi Antonella, Burchielli Emanuela, Perruccio Katia, Aversa Franco, Martelli Massimo F
Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Ospedale Santa Maria della Misericordia, Perugia, Italy.
Semin Immunopathol. 2008 Dec;30(4):489-503. doi: 10.1007/s00281-008-0136-1. Epub 2008 Nov 11.
Although the optimal donor for allogeneic hematopoietic stem cell transplantation is a human leukocyte antigen (HLA)-matched sibling, 75% of patients do not have a match and alternatives are matched unrelated volunteers, unrelated umbilical cord blood units, and full HLA-haplotype-mismatched family members. This review will focus on the open issues of allogeneic hematopoietic transplantation and on the benefits of natural killer (NK) cell alloreactivity and its underlying mechanisms. Donor-versus-recipient NK cell alloreactivity derives from a mismatch between inhibitory receptors for self major histocompatibility complex (MHC) class I molecules on donor NK clones and the MHC class I ligands on recipient cells. These NK clones sense the missing expression of the self MHC class I allele on the allogeneic targets ("missing self") and mediate alloreactions. Here, we review the translation of NK cell allorecognition into the clinical practice of allogeneic hematopoietic transplantation and discuss how it has opened innovative perspectives in the cure of leukemia.
尽管异基因造血干细胞移植的最佳供体是人类白细胞抗原（HLA）匹配的同胞，但75%的患者没有匹配的供体，替代方案包括匹配的无关志愿者、无关脐血单位以及HLA单倍型完全不匹配的家庭成员。本综述将聚焦于异基因造血移植的未决问题，以及自然杀伤（NK）细胞同种异体反应性的益处及其潜在机制。供体与受体的NK细胞同种异体反应性源于供体NK克隆上自身主要组织相容性复合体（MHC）I类分子抑制性受体与受体细胞上MHC I类配体之间的不匹配。这些NK克隆感知到同种异体靶标上自身MHC I类等位基因的缺失表达（“缺失自我”）并介导同种异体反应。在此，我们综述了NK细胞同种异体识别在异基因造血移植临床实践中的转化，并讨论了它如何为白血病治疗开辟了创新视角。
