Decreased percentage of CD4+FoxP3+ cells in bronchoalveolar lavage from lung transplant recipients correlates with development of bronchiolitis obliterans syndrome.
Decreased percentage of CD4+FoxP3+ cells in bronchoalveolar lavage from lung transplant recipients correlates with development of bronchiolitis obliterans syndrome.
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DOI：
10.1097/tp.0b013e3181e8dabe
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发表时间：
2010-09-15
期刊：
影响因子：
6.2
通讯作者：
Alegre ML
中科院分区：
文献类型：
--
作者：
Bhorade SM;Chen H;Molinero L;Liao C;Garrity ER;Vigneswaran WT;Shilling R;Sperling A;Chong A;Alegre ML
在患有终末期肺病的患者中，肺移植受到慢性排斥反应的限制，慢性排斥反应的发生率和严重程度超过大多数其他移植器官。同种异体免疫反应在表现为闭塞性细支气管炎综合征（BOS）的慢性排斥反应进展中起重要作用，但目前没有生物标志物可以预测BOS的进展。动物模型的研究表明，移植物内调节性T细胞（TCRs）在维持移植耐受中是重要的，FoxP 3是原型Treg标志物。采用流式细胞术比较14例稳定期肺移植受者和6例最终发生BOS的肺移植受者血液和支气管肺泡灌洗液（BAL）中白细胞FoxP 3的表达。与随后发展为BOS的患者相比，稳定患者的BAL中CD 4+细胞中FoxP 3+细胞的百分比显著增加，Treg吸引趋化因子CCL 22的水平更高。在急性排斥反应（AR）时，有限的序贯分析显示，未进展为BOS的患者中BAL CD 4 + FoxP 3+细胞的百分比较高。在这项初步研究中，BAL中3.2%的CD 4 +/FoxP 3+细胞的阈值区分了移植后前两年内稳定的受体和随后发生BOS的受体。因此，BALF中FoxP 3+细胞在CD 4+细胞中的比例可能有助于预测肺移植的结果，并指导肺移植受者的治疗性免疫抑制。
Lung transplantation, in patients with end-stage lung disease, is limited by chronic rejection which occurs with an incidence and severity exceeding most other transplanted organs. Alloimmune responses play an important role in progression to chronic rejection that manifests as bronchiolitis obliterans syndrome (BOS), but no biomarker can currently predict the progression to BOS. Studies in animal models suggest that intra-graft T regulatory cells (Tregs) are important in maintaining transplantation tolerance and FoxP3 is the protoypic Treg marker. Leukocytes in blood and bronchoalveolar lavage fluid (BAL) were compared for expression of FoxP3 by flow cytometry in 14 stable lung transplant recipients and 6 lung transplant recipients who eventually developed BOS. Stable patients had a significantly increased percentage of FoxP3+ cells among CD4+ cells in BAL and greater levels of the Treg-attracting chemokine CCL22, than patients who subsequently developed BOS. At the time of acute rejection (AR), limited sequential analyses revealed a higher percentage of BAL CD4+FoxP3+ cells in patients who did not progress to BOS. In this pilot study, a threshold of 3.2% CD4+/FoxP3+ cells in the BAL distinguished stable recipients from those developing BOS subsequently within the first two years post transplantation. Thus, the proportion of FoxP3+ cells among CD4+ cells in BAL may help predict lung allograft outcome and guide therapeutic immunosuppression in lung transplant recipients.