Suárez-Álvarez Beatriz, Fernández-Sánchez Alba, López-Vázquez Antonio, Coto Eliecer, Ortega Francisco, López-Larrea Carlos
Department of Immunology, Hospital Universitario Central de Asturias , Oviedo, Spain.
Department of Molecular Genetics, Hospital Universitario Central de Asturias , Oviedo, Spain ; Fundación Renal 'Iñigo Alvarez de Toledo' , Madrid, Spain.
Kidney Int Suppl (2011). 2011 Aug;1(2):52-57. doi: 10.1038/kisup.2011.13.
The role of natural killer (NK) cells in solid organ transplantation is not well established, although several recent reports highlight the importance of the activating receptor NKG2D and its ligands in the development of rejection during transplantation. The human NKG2D ligands (MICA and MICB) are induced in allografts during acute and chronic rejection, and the presence of anti-MICA antibodies is correlated with a higher incidence of rejection. The binding of these ligands to its receptor NKG2D activates NK cells, enhances the functions of effectors, and allows NK cells to function as a bridge between innate and adaptive immunity associated with the transplantation. In fact, blockage of NKG2D with the anti-NKG2D monoclonal antibodies prolongs graft survival and prevents CD28-independent rejection in heart and skin allograft mouse models. Furthermore, the current immunosuppressive therapies can modulate the expression of NK cell receptors and consequently the effector functions of NK cells. That is particularly important during the first few months after transplantation, when the susceptibility to opportunistic viral infections is higher and NKG2D has an essential role. In this review, we analyze in detail the potential role of the NKG2D-activating receptor and its ligands in the immune responses during the outcome of solid organ transplantation. These findings open a new pathway for therapeutic intervention that can contribute to tolerance in solid organ transplantation.
自然杀伤（NK）细胞在实体器官移植中的作用尚未完全明确，尽管最近有几份报告强调了激活受体NKG2D及其配体在移植排斥反应发生过程中的重要性。人类NKG2D配体（MICA和MICB）在急性和慢性排斥反应期间的同种异体移植物中被诱导产生，并且抗MICA抗体的存在与更高的排斥发生率相关。这些配体与其受体NKG2D的结合激活NK细胞，增强效应器功能，并使NK细胞能够作为与移植相关的固有免疫和适应性免疫之间的桥梁发挥作用。事实上，在心脏和皮肤同种异体移植小鼠模型中，用抗NKG2D单克隆抗体阻断NKG2D可延长移植物存活时间并防止不依赖CD28的排斥反应。此外，当前的免疫抑制疗法可以调节NK细胞受体的表达，从而调节NK细胞的效应器功能。这在移植后的最初几个月尤为重要，因为此时发生机会性病毒感染的易感性较高，且NKG2D起着至关重要的作用。在本综述中，我们详细分析了NKG2D激活受体及其配体在实体器官移植结果过程中的免疫反应中的潜在作用。这些发现为治疗干预开辟了一条新途径，有助于实现实体器官移植中的免疫耐受。
