Immunosenescence, the age-related dysregulation of innate and adaptive immunity, impairs immune response and increases inflammation, leading to higher infection and cardiovascular risks, particularly outside the field of transplantation. In kidney transplant recipients (KTRs), conditions like cytomegalovirus infection, old age, uremia, smoking, and diabetes, linked to poor outcomes, are associated with enhanced immunosenescence. Recent studies highlight the pathogenic role of cytotoxic T cells, particularly terminally differentiated effector memory T cells that reexpress CD45RA (TEMRA), in graft dysfunction. A higher proportion of circulating CD8+ TEMRA cells is observed in KTRs with chronic rejection. In antibody-mediated rejection, they invade the graft by superior chemotactic properties and binding to human leukocyte antigen (HLA) antibodies through FcγRIIIa (CD16). Also in microvascular inflammation without donor-specific antibodies, and even in patients without rejection but faster decline of kidney function, intragraft CD8+ TEMRA cells were instrumental. CD8+ TEMRA cells may explain the unresolved dismal graft outcomes associated with donor age and cytomegalovirus-serostatus mismatching and could become a novel therapeutic target in KTRs.

中文翻译：

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肾移植受者终末分化效应记忆 T 细胞：新的十字路口


免疫衰老是与年龄相关的先天免疫和适应性免疫失调，会损害免疫反应并增加炎症，从而导致更高的感染和心血管风险，尤其是在移植领域之外。在肾移植受者 （KTR） 中，与不良结果相关的巨细胞病毒感染、老年、尿毒症、吸烟和糖尿病等疾病与免疫衰老增强有关。最近的研究强调了细胞毒性 T 细胞的致病作用，特别是重新表达 CD45RA （TEMRA） 的终末分化效应记忆 T 细胞，在移植物功能障碍中的作用。在慢性排斥反应的 KTR 中观察到更高比例的循环 CD8 + TEMRA 细胞。在抗体介导的排斥反应中，它们通过卓越的趋化特性侵入移植物，并通过 FcγRIIIa （CD16） 与人类白细胞抗原 （HLA） 抗体结合。同样在没有供体特异性抗体的微血管炎症中，甚至在没有排斥反应但肾功能下降更快的患者中，移植物内 CD8 + TEMRA 细胞是有用的。CD8 + TEMRA 细胞可以解释与供体年龄和巨细胞病毒血清状态不匹配相关的未解决的令人沮丧的移植物结果，并可能成为 KTR 中的新治疗靶点。