Regulatory, Effector, and Cytotoxic T Cell Profiles in Long-Term Kidney Transplant Patients
Regulatory, Effector, and Cytotoxic T Cell Profiles in Long-Term Kidney Transplant Patients
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DOI：
10.1681/asn.2008050450
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发表时间：
2009-05-01
影响因子：
13.6
通讯作者：
Soulillou, Jean-Paul
中科院分区：
文献类型：
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作者：
Ashton-Chess, Joanna;Dugast, Emilie;Soulillou, Jean-Paul
动物研究表明，调节性T细胞（T细胞）在同种异体移植耐受中的潜在作用，但这些FOXP 3+细胞似乎是人类肾移植受者急性排斥反应（AR）的固有组成部分。调节细胞和效应细胞/细胞毒性细胞之间的平衡可能决定移植物的结果，这种平衡尚未被描述为慢性同种异体移植物损伤。我们研究了关键的调节、效应和细胞毒性转录物（即，FOXP 3、T-bet和颗粒酶B）。我们发现，尽管移植物内或外周血FOXP 3或T-bet mRNA都不能区分排斥和非排斥状态，但颗粒酶B（Grz B）mRNA可以：在慢性抗体介导的排斥（CAMR）患者的移植物中显著增加，外周血中显著减少。定量外周血GrzB mRNA表现出潜在的帮助CAMR的非侵入性诊断。总之，这些数据证实GrzB不仅是AR的标志物，也是CAMR的标志物。此外，我们确定了几个以前未报告的临床或人口统计学因素影响的监管/效应/细胞毒性在外周血中的配置文件，强调有必要考虑混杂变量时，考虑使用潜在的生物标志物，如FOXP 3，在肾移植的诊断或预后。
Animal studies have suggested a potential role for regulatory T cells (Tregs) in allograft tolerance, but these FOXP3+ cells seem to be an inherent component of acute rejection (AR) in human recipients of renal transplants. The balance between regulatory cells and effector/cytotoxic cells may determine graft outcome; this balance has not been described for chronic allograft injury. We investigated the expression of key regulatory, effector, and cytotoxic transcripts (i.e., FOXP3, T-bet, and granzyme B, respectively) in the grafts and peripheral blood of long-term-surviving renal transplant patients. We found that, whereas neither intragraft nor peripheral blood FOXP3 or T-bet mRNA could distinguish between rejection and nonrejection status, granzyme B (GrzB) mRNA could: It was significantly increased in the graft and significantly decreased in the peripheral blood of patients with chronic antibody-mediated rejection (CAMR). Quantifying peripheral blood GrzB mRNA demonstrated potential to aid in the noninvasive diagnosis of CAMR. In summary, these data affirm GrzB as a marker not only for AR but also for CAMR. In addition, we identified several previously unreported clinical or demographic factors influencing regulatory/effector/cytotoxic profiles in the peripheral blood, highlighting the necessity to consider confounding variables when considering the use of potential biomarkers, such as FOXP3, for diagnosis or prognosis in kidney transplantation.