Increased expression of cytotoxic effector molecules: Different interpretations for steroid‐based and steroid‐free immunosuppression
Increased expression of cytotoxic effector molecules: Different interpretations for steroid‐based and steroid‐free immunosuppression
复制标题
细胞毒性效应分子表达增加：对类固醇和无类固醇免疫抑制的不同解释
作者：
Thomas S. Satterwhite;M. Chua;S. Hsieh;Stella L Chang;J. Scandling;O. Salvatierra;M. Sarwal
摘要：细胞毒性T淋巴细胞（CTL）效应分子作为类固醇免疫抑制肾移植受体急性排斥反应的标志物已被研究。我们假设基础CTL基因表达可能随着移植后的时间以及不同的免疫抑制方案（基于类固醇或不使用类固醇）而变化。因此，CTL基因表达的变化可能影响预测急性同种异体移植排斥反应的能力。我们使用非侵入性的定量竞争-逆转录-聚合酶链反应（QC - RT - PCR）方法来定量来自无类固醇和基于类固醇的成人和儿童肾移植受体的外周血淋巴细胞（PBL）样本中CTL效应分子（颗粒素，GL；穿孔素，P；颗粒酶B， GB）的数量。在一项单独的临床研究中，两种方案的患者在移植后1、3、6和12个月通过方案活检进行临床监测，并在移植后1年进行移植物功能监测。移植功能稳定的无类固醇患者在移植后GL、P和GB基因表达随时间增加，主要在移植后第一个月增加。在没有急性排斥反应的移植后第一年末，GL表达进一步增加，而GB和P水平不变。在移植后的比较时间点上，与具有临床稳定移植功能或急性排斥反应的类固醇受体相比，未使用类固醇且移植物功能稳定的患者的CTL基因水平更高。这项研究表明，尽管CTL基因表达水平在以类固醇为基础的方案中对监测急性排斥反应的风险很重要，但可能不适用于无类固醇免疫抑制的患者。无类固醇患者早期水平升高似乎与完全不使用类固醇相关。由于无类固醇患者似乎在1年内具有较低的急性排斥发生率和较好的长期移植物功能，在没有急性排斥的情况下，CTL基因的早期增加可能表明早期适应性免疫激活反应，促进该方案中的早期移植物接受。
Abstract: Cytotoxic T lymphocyte (CTL) effector molecules have been studied as markers of acute rejection in renal allograft recipients on steroid‐based immunosuppression. We hypothesized that basal CTL gene expression may vary with time post‐transplantation as well as with different immunosuppression protocols (steroid‐based or steroid‐free). Variations in CTL gene expression may thus impact on the ability to predict acute allograft rejection. We used the non‐invasive method of quantitative competitive‐reverse transcription‐polymerase chain reaction (QC‐RT‐PCR) to quantify the amounts of CTL effector molecules (granulysin, GL; perforin, P; granzyme B, GB) in serial peripheral blood lymphocyte (PBL) samples from steroid‐free and steroid‐based adult and pediatric renal allograft recipients. Patients on both protocols were clinically monitored by protocol biopsies at 1, 3, 6, and 12 months post‐transplantation and for graft function at 1 yr post‐transplantation in a separate clinical study. Steroid‐free patients with stable graft function showed an increase in GL, P, and GB gene expression over time post‐transplantation with the increase being seen largely by the first post‐transplant month. A further increase in GL expression was noted at the end of the first post‐transplant year in the absence of acute rejection, whereas GB and P levels were unchanged. At comparative time‐points post‐transplantation, CTL genes were found to be higher in steroid‐free patients with stable graft function, compared to steroid‐based recipients with either clinically stable graft function or acute rejection. This study suggests that levels of CTL gene expression, although important in a steroid‐based regimen to monitor the risk of acute rejection, may not be similarly applied in patients on steroid‐free immunosuppression. The early increase in levels seen in steroid‐free patients appears to correlate with the total absence of steroids. As steroid‐free patients seem to have a lower incidence of acute rejection and better long‐term graft function at 1 yr, the early increase in CTL genes in the absence of acute rejection may suggest an early adaptive immune activation response, promoting early graft acceptance in this protocol.
影响因子：
6.2
作者：
Vasconcellos, LM;Asher, F;Strom, TB
通讯作者：
Strom, TB