INSERM, UMR1098, Federation Hospitalo-Universitaire INCREASE, Besançon, France; Université de Franche-Comté, Faculté de Médecine et de Pharmacie, Besançon, France; Structure Fédérative de Recherche, SFR FED4234, Besançon, France; CHU Besançon, Department of Nephrology, Dialysis, and Renal Transplantation, Besançon, France.
Am J Transplant. 2015 Apr;15(4):1028-38. doi: 10.1111/ajt.13092. Epub 2015 Mar 10.
Persistent ATG-induced CD4(+) T cell lymphopenia is associated with serious clinical complications. We tested the hypothesis that ATG induces accelerated immune senescence in renal transplant recipients (RTR). Immune senescence biomarkers were analyzed at transplant and one-year later in 97 incident RTR -62 patients receiving ATG and 35 receiving anti-CD25 mAb (α-CD25). This consisted in: (i) thymic output; (ii) bone marrow renewal of CD34(+) hematopoietic progenitor cells (CD34(+) HPC) and lymphoid (l-HPC) and myeloid (m-HPC) progenitor ratio; (iii) T cell phenotype; and (iv) measurement of T cell relative telomere length (RTL) and telomerase activity (RTA). Clinical correlates were analyzed with a 3 year follow-up. Thymic output significantly decreased one-year posttransplant in ATG-treated patients. ATG was associated with a significant decrease in l-HPC/m-HPC ratio. Late stage differentiated CD57(+) /CD28(-) T cells increased in ATG-treated patients. One-year posttransplant T cell RTL and RTA were consequently lower in ATG-treated patients. ATG is associated with accelerated immune senescence. Increased frequency of late differentiated CD4(+) T cell frequency at transplantation tended to be predictive of a higher risk of subsequent opportunistic infections and of acute rejection only in ATG-treated patients but this needs confirmation. Considering pretransplant immune profile may help to select those patients who may benefit from ATG to prevent severe infections and acute rejection.
持续的 ATG 诱导的 CD4(+)T 细胞淋巴细胞减少与严重的临床并发症有关。我们检验了这样一个假设，即 ATG 会导致肾移植受者（RTR）的免疫衰老加速。在 97 例接受 ATG 治疗和 35 例接受抗-CD25 mAb（α-CD25）治疗的 RTR 患者中，在移植时和一年后检测了免疫衰老生物标志物 -62 例患者。这包括：（i）胸腺输出；（ii）骨髓更新 CD34(+)造血祖细胞（CD34(+)HPC）和淋巴样（l-HPC）和髓样（m-HPC）祖细胞的比例；（iii）T 细胞表型；以及（iv）测量 T 细胞相对端粒长度（RTL）和端粒酶活性（RTA）。用 3 年的随访分析了临床相关性。在接受 ATG 治疗的患者中，移植后一年胸腺输出显著下降。ATG 与 l-HPC/m-HPC 比例显著下降有关。晚期分化的 CD57(+) / CD28(-)T 细胞在接受 ATG 治疗的患者中增加。因此，接受 ATG 治疗的患者在移植后一年的 T 细胞 RTL 和 RTA 较低。ATG 与免疫衰老加速有关。移植时晚期分化的 CD4(+)T 细胞频率增加，预示着接受 ATG 治疗的患者随后发生机会性感染和急性排斥反应的风险较高，但这需要进一步证实。考虑到移植前的免疫特征可能有助于选择那些可能从 ATG 中获益以预防严重感染和急性排斥反应的患者。
