He An, Yang Yiren, Kotsch Katja, Sattler Arne
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department for General and Visceral Surgery, Berlin, Germany.
Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Transpl Int. 2025 Jan 7;37:13997. doi: 10.3389/ti.2024.13997. eCollection 2024.
Kidney transplantation is the treatment of choice for end-stage organ failure. To improve transplantation outcomes, particularly of "marginal" organs from extended criteria donors (ECD), attempts have been made to therapeutically modulate donor or graft pre-transplantation. Anti-thymocyte globulin (ATG) has a history as lymphocyte-depleting, immunosuppressive drug for treating rejection episodes post transplantation. In this study, however, we aimed to comprehensively analyze the effects of ATG donor pre-conditioning in a mouse model of kidney transplantation. ATG pre-treatment of potential donors led to a broad depletion of T- and NK cells in peripheral blood, non-lymphoid (including kidney) and lymphoid organs within 48 h, whereas myeloid cells were spared. ATG was also effectively depleting renal innate lymphoid type 1 and 2 cells. Importantly, transplantation of kidneys from ATG pre-treated donors into fully mismatched recipients showed only mild effects on leukocyte re-composition post transplantation. In line with this, serum creatinine and urea levels were similar in animals receiving kidneys from ATG treated donors or controls, demonstrating that donor treatment had no effect on allograft function in the early post-transplantation phase. In summary, our findings are suggestive of a more cell-type-specific depletion strategy in concert with an experimental model better reflecting aspects of clinical transplantation.
肾移植是终末期器官衰竭的首选治疗方法。为了改善移植效果，尤其是来自扩大标准供体（ECD）的“边缘”器官的移植效果，人们尝试在移植前对供体或移植物进行治疗性调节。抗胸腺细胞球蛋白（ATG）作为一种淋巴细胞清除、免疫抑制药物，用于治疗移植后排斥反应已有一定历史。然而，在本研究中，我们旨在全面分析ATG预处理供体在小鼠肾移植模型中的效果。对潜在供体进行ATG预处理会导致外周血、非淋巴组织（包括肾脏）和淋巴器官中的T细胞和NK细胞在48小时内广泛减少，而髓样细胞则不受影响。ATG还能有效清除肾脏中的1型和2型固有淋巴细胞。重要的是，将经ATG预处理供体的肾脏移植到完全不匹配的受体中，对移植后白细胞重新组成的影响仅为轻度。与此一致的是，接受经ATG处理供体肾脏的动物与对照组动物的血清肌酐和尿素水平相似，这表明供体处理在移植后早期对同种异体移植功能没有影响。总之，我们的研究结果提示，应采用一种更具细胞类型特异性的清除策略，并结合一个能更好反映临床移植各方面情况的实验模型。
