Department of 1st Urology Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Front Immunol. 2024 Aug 6;15:1418238. doi: 10.3389/fimmu.2024.1418238. eCollection 2024.
Renal transplantation is a life-saving treatment for patients with end-stage renal disease. However, the challenge of transplant rejection and the complications associated with immunosuppressants necessitates a deeper understanding of the underlying immune mechanisms. T cell exhaustion, a state characterized by impaired effector functions and sustained expression of inhibitory receptors, plays a dual role in renal transplantation. While moderate T cell exhaustion can aid in graft acceptance by regulating alloreactive T cell responses, excessive exhaustion may impair the recipient's ability to control viral infections and tumors, posing significant health risks. Moreover, drugs targeting T cell exhaustion to promote graft tolerance and using immune checkpoint inhibitors for cancer treatment in transplant recipients are areas deserving of further attention and research. This review aims to provide a comprehensive understanding of the changes in T cell exhaustion levels after renal transplantation and their implications for graft survival and patient outcomes. We discuss the molecular mechanisms underlying T cell exhaustion, the role of specific exhaustion markers, the potential impact of immunosuppressive therapies, and the pharmaceutical intervention on T cell exhaustion levels. Additionally, we demonstrate the potential to modulate T cell exhaustion favorably, enhancing graft survival. Future research should focus on the distinctions of T cell exhaustion across different immune states and subsets, as well as the interactions between exhausted T cells and other immune cells. Understanding these dynamics is crucial for optimizing transplant outcomes and ensuring long-term graft survival while maintaining immune competence.
肾移植是治疗终末期肾病患者的一种救命疗法。然而，移植排斥反应的挑战以及免疫抑制剂相关的并发症，需要我们深入了解潜在的免疫机制。T 细胞耗竭是一种特征为效应功能受损和持续表达抑制性受体的状态，在肾移植中发挥着双重作用。适度的 T 细胞耗竭可以通过调节同种反应性 T 细胞反应来帮助接受移植物，但过度的耗竭可能会损害受者控制病毒感染和肿瘤的能力，带来重大健康风险。此外，针对 T 细胞耗竭的药物以促进移植物耐受，以及在移植受者中使用免疫检查点抑制剂治疗癌症，是值得进一步关注和研究的领域。本综述旨在全面了解肾移植后 T 细胞耗竭水平的变化及其对移植物存活和患者结局的影响。我们讨论了 T 细胞耗竭的分子机制、特定耗竭标志物的作用、免疫抑制治疗的潜在影响以及对 T 细胞耗竭水平的药物干预。此外，我们还展示了有利地调节 T 细胞耗竭的潜力，从而提高移植物的存活率。未来的研究应侧重于不同免疫状态和亚群之间 T 细胞耗竭的区别，以及耗竭的 T 细胞与其他免疫细胞之间的相互作用。了解这些动态对于优化移植结果和确保长期移植物存活以及维持免疫能力至关重要。
