Renal Transplant Unit, University of Leeds, Leeds, UK.
Am J Transplant. 2012 Apr;12(4):919-31. doi: 10.1111/j.1600-6143.2011.03891.x. Epub 2012 Mar 5.
Several studies have analyzed the phenotype of repopulated T-lymphocytes following alemtuzumab induction; however there has been less scrutiny of the reconstituted B-cell compartment. In the context of a randomized controlled trial (RCT) comparing alemtuzumab induction with tacrolimus monotherapy against basiliximab induction with tacrolimus and mycophenolate mofetil (MMF) therapy in renal transplantation, we analyzed the peripheral B- and T-lymphocyte phenotypes of patients at a mean of 25 +/- 2 months after transplantation. We examined the relationship between peripheral lymphocyte phenotype and graft function. Patients who received alemtuzumab had significantly higher numbers of B cells including naïve, transitional and regulatory subsets. In contrast, the CD4(+) T-cell compartment was dominated by a memory cell phenotype. Following either basiliximab or alemtuzumab induction patients with lower numbers of B cells or B subsets had significantly worse graft function. For alemtuzumab there was also a correlation between these subsets the stability of graft function and the presence of HLA-specific antibodies. These results demonstrate that a significant expansion of regulatory type B cells is associated with superior graft function and that this pattern is more common after alemtuzumab induction. This phenomenon requires further prospective study to see whether this phenotype could be used to customize immunotherapy.
几项研究分析了阿仑单抗诱导后再殖 T 淋巴细胞的表型;然而,对再殖 B 细胞区室的研究较少。在一项比较阿仑单抗诱导与他克莫司单药治疗与巴利昔单抗诱导联合他克莫司和霉酚酸酯(MMF)治疗肾移植的随机对照试验(RCT)中,我们分析了移植后平均 25 +/- 2 个月时患者的外周 B 和 T 淋巴细胞表型。我们研究了外周淋巴细胞表型与移植物功能之间的关系。接受阿仑单抗治疗的患者具有明显更高数量的 B 细胞,包括幼稚、过渡和调节亚群。相比之下,CD4(+) T 细胞区室以记忆细胞表型为主。在接受巴利昔单抗或阿仑单抗诱导的患者中,B 细胞或 B 细胞亚群数量较少的患者,移植物功能明显较差。对于阿仑单抗,这些亚群与移植物功能的稳定性和 HLA 特异性抗体之间也存在相关性。这些结果表明,调节型 B 细胞的显著扩增与更好的移植物功能相关,并且这种模式在阿仑单抗诱导后更为常见。这种现象需要进一步的前瞻性研究,以确定这种表型是否可用于定制免疫治疗。