异基因造血干细胞移植中杀伤细胞抑制性受体(KIR)在GVHD和GVL发生中的作用(英文)

Killer Cell Inhibitory Receptors Involved in Graft-Versus-Host Disease and Graft-Versus-Leukemia Effect in Allogeneic Hematopoietic Stem Cell Transplantation——Review

杀伤细胞抑制性受体 (KIR)属于免疫球蛋白超家族成员I型跨膜蛋白分子 ,主要表达于人NK细胞和某些T淋巴细胞。它们的配体为HLAⅠ类分子。当KIR所识别的MHC配体缺失时 ,即表现为对靶细胞的杀伤作用 (所谓丢失自我“missing self”机制 )。已证实 ,NK细胞和T细胞的KIR分子与靶细胞的MHC分子特异性的识别机制参与移植物抗宿主病 (GVHD)的发生并且影响移植物抗白血病 (GVL)作用。KIR的存在可能是免疫活性细胞不攻击自身组织的主要机制。KIR基因家族及其配体HLA C分子均具有基因多态性 ,因此在HLA相合和不全相合的异基因造血干细胞移植中 ,供受者KIR基因表达的差异在一定程度上影响移植效果。本文主要就KIR如何影响异基因造血干细胞移植后GVHD和GVL进行综述。

Killer cell inhibitory receptors (KIR) are members of the immunoglobulin superfamily (Ig SF) and transmembrane molecules type I expressed on human natural killer cells and some T lymphocytes. They are ligands for HLA class I antigens. According to the 'missing self' hypothesis, KIR deliver inhibitory signals that prevent target cell lysis upon binding to the self MHC class I antigens. KIR regulates NK cell function concerned with the control graft versus host disease (GVHD) and graft versus leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation (HSCT). The KIR repertoire is substantially influenced by the polymorphic and polygeneic nature of the KIR gene family, and there exist the polymorphism of KIR ligands mainly HLA C molecule. So it is difficult to achieve the beneficial effect of NK cells on the outcome of partly HLA mismatched hematopoietic cell transplantation. This review aims to provide background and previous observations on the KIRs which are thought to influence the outcome of HSCT.