The biological functions of NK cells and their roles in transplant immunology

doi:10.3877/cma.j.issn.1674-3903.2026.02.011

Abstract

Abstract:

As a key component of the innate immune system, natural killer (NK) cells play a central role in human immune defense, and immunomodulatory agents and immunosuppressive regimens administered to organ transplant recipients may significantly affect their functions and biological effects. Clarifying the dual roles of NK cells and the potential impact of immunosuppressive therapies on their functions is particularly critical for infection prevention and management in this patient population. This review comprehensively explores the multifaceted involvement of NK cells in transplantation immunology, evaluates the effects of immunosuppression on NK cell activity, and provides valuable references for future studies focusing on the anti-infective capabilities of NK cells and their roles in immune signaling pathways in the context of transplantation medicine.

Key words: Natural killer cell, Organ transplantation, Immunosuppression, Allograft rejection

Bin Su, Yuan Xu, Haiyang Li, Shuang Hou. The biological functions of NK cells and their roles in transplant immunology[J]. Chinese Journal of Transplantation(Electronic Edition), 2026, 20(02): 132-136.

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URL: https://zhyzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-3903.2026.02.011

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药物类别	代表药物	作用机制	对NK细胞的影响
CNI	环孢素、他克莫司	干扰钙调磷酸酶依赖的信号通路	抑制NK细胞脱颗粒，减少IFN-γ分泌，降低抗感染能力
mTOR抑制剂	西罗莫司、依维莫司	阻断mTOR相关信号通路	抑制NKG2A/NCR表达，削弱细胞毒性；抑制CD56^bright亚群增殖
霉酚酸类药物	MMF、MPA	抑制IMPDH，阻断鸟苷核苷酸合成	降低CD56表达，抑制增殖和IFN-γ产生
糖皮质激素	泼尼松、地塞米松	结合糖皮质激素受体，抑制NF-κB/AP-1等转录因子	减少NK细胞数量，下调活化受体表达，调节活化/抑制受体平衡，降低溶细胞活性
抗CD20单抗	利妥昔单抗	靶向CD20，介导ADCC	可增强NK细胞介导的ADCC效应；与IL-15联用时可能进一步提高NK细胞活性；联用PD-L1抑制剂可调节CD16A/CD137相关信号通路
抗EGFR单抗	西妥昔单抗	靶向EGFR，激活CD16A，介导ADCC	通过Fc γ受体Ⅲa增强ADCC杀伤能力，疗效受Fc γ受体Ⅲa-V158F基因多态性影响；联用PD-L1抑制剂改善NK细胞功能
抗NKG2A单抗	莫那利珠单抗	阻断NKG2A抑制信号	解除NK细胞抑制，增强其活性；联合疗法(如PD-L1抑制剂)可能提高临床疗效

药物类别	代表药物	作用机制	对NK细胞的影响
CNI	环孢素、他克莫司	干扰钙调磷酸酶依赖的信号通路	抑制NK细胞脱颗粒，减少IFN-γ分泌，降低抗感染能力
mTOR抑制剂	西罗莫司、依维莫司	阻断mTOR相关信号通路	抑制NKG2A/NCR表达，削弱细胞毒性；抑制CD56^bright亚群增殖
霉酚酸类药物	MMF、MPA	抑制IMPDH，阻断鸟苷核苷酸合成	降低CD56表达，抑制增殖和IFN-γ产生
糖皮质激素	泼尼松、地塞米松	结合糖皮质激素受体，抑制NF-κB/AP-1等转录因子	减少NK细胞数量，下调活化受体表达，调节活化/抑制受体平衡，降低溶细胞活性
抗CD20单抗	利妥昔单抗	靶向CD20，介导ADCC	可增强NK细胞介导的ADCC效应；与IL-15联用时可能进一步提高NK细胞活性；联用PD-L1抑制剂可调节CD16A/CD137相关信号通路
抗EGFR单抗	西妥昔单抗	靶向EGFR，激活CD16A，介导ADCC	通过Fc γ受体Ⅲa增强ADCC杀伤能力，疗效受Fc γ受体Ⅲa-V158F基因多态性影响；联用PD-L1抑制剂改善NK细胞功能
抗NKG2A单抗	莫那利珠单抗	阻断NKG2A抑制信号	解除NK细胞抑制，增强其活性；联合疗法(如PD-L1抑制剂)可能提高临床疗效

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