Lederer Stephan R, Friedrich Nicole, Gruber Rudolf, Landgraf Rüdiger, Toepfer Marcel, Sitter Thomas
Medizinische Klinik, Innenstadt, Klinikum der Universität München, München, Deutschland.
Int Arch Allergy Immunol. 2004 Mar;133(3):276-84. doi: 10.1159/000076835. Epub 2004 Feb 17.
The CD40-CD40L (CD154) costimulatory pathway plays a critical role in the pathogenesis of kidney allograft rejection. In renal transplant biopsies, CD4+CD40L+ graft-infiltrating cells were detected during chronic rejection in contrast to acute rejection episodes. Using a rapid noninvasive FACS procedure, we were able to demonstrate CD40L upregulation in peripheral blood of patients with chronic renal allograft dysfunction.
Whole blood from recipients of renal allografts was stimulated with PMA and ionomycin and measured by flow cytometry. Patients were assigned to three groups based on transplant function. Group 1: 26 patients with excellent renal transplant function; group 2: 28 patients with impaired transplant function; group 3: 14 patients with chronic allograft dysfunction and group 4: 8 healthy controls.
The median percentage +/- SEM of CD4+/CD40L+ cells stimulated ex vivo at 10 ng/ml PMA was as follows: group 1: 28.3 +/- 4.1%; group 2: 18.4 +/- 2.4%; group 3: 50.1 +/- 5.0% and group 4: 40.4 +/- 3.4%. Subdivisions of groups 2 and 3 resulted in different CD40L expression patterns. Patients with increased serum creatinine since the initial phase after transplantation (groups 2a and 3a) revealed a higher percentage of CD4+CD40L+ cells than patients showing a gradual increase over time (groups 2b and 3b). Consequently, patients of group 3a exhibited a significantly reduced transplant function compared with those of group 3b.
After PMA + ionomycin stimulation, patients with excellent kidney graft function displayed significantly reduced expression of CD40L surface molecules on CD4+ cells early after transplantation. Those with a chronic dysfunction of the renal graft showed significantly more CD4+ cells expressing CD40L compared to the other transplanted groups. These results demonstrate that the percentage of CD4+CD40L+ cells stimulated ex vivo in peripheral blood may be a valuable marker for chronic allograft nephropathy.
CD40 - CD40L（CD154）共刺激通路在肾移植排斥反应的发病机制中起关键作用。在肾移植活检中，与急性排斥反应发作相比，慢性排斥反应期间检测到CD4 + CD40L +移植物浸润细胞。使用快速非侵入性流式细胞术程序，我们能够证明慢性肾移植功能障碍患者外周血中CD40L上调。
用佛波酯（PMA）和离子霉素刺激肾移植受者的全血，并通过流式细胞术进行检测。根据移植功能将患者分为三组。第1组：26例肾移植功能良好的患者；第2组：28例移植功能受损的患者；第3组：14例慢性移植物功能障碍患者；第4组：8例健康对照者。
在10 ng/ml PMA体外刺激下，CD4 + /CD40L +细胞的中位百分比±标准误如下：第1组：28.3±4.1%；第2组：18.4±2.4%；第3组：50.1±5.0%；第4组：40.4±3.4%。第2组和第3组的细分导致不同的CD40L表达模式。自移植后初始阶段血清肌酐升高的患者（第2a组和第3a组）显示CD4 + CD40L +细胞的百分比高于随时间逐渐升高的患者（第2b组和第3b组）。因此，与第3b组患者相比，第3a组患者的移植功能显著降低。
经PMA +离子霉素刺激后，肾移植功能良好的患者在移植后早期CD4 +细胞上CD40L表面分子的表达显著降低。与其他移植组相比，肾移植慢性功能障碍患者显示出更多表达CD40L的CD4 +细胞。这些结果表明，外周血中体外刺激的CD4 + CD40L +细胞百分比可能是慢性移植物肾病的一个有价值的标志物。
