Th-17, monokines, collagen type V, and primary graft dysfunction in lung transplantation
Th-17, monokines, collagen type V, and primary graft dysfunction in lung transplantation
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DOI：
10.1164/rccm.200612-1901oc
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发表时间：
2008-03-15
影响因子：
24.7
通讯作者：
Wilkes, David S.
中科院分区：
文献类型：
--
作者：
Bobadilla, Joseph L.;Love, Robert B.;Wilkes, David S.
原理：原发性移植物功能障碍（PGD）是肺移植的一种严重并发症，其发病机制尚不清楚。人类研究和啮齿动物模型表明，胶原V（col[V]），刺激IL-17依赖性细胞免疫后，肺transplantation.Objectives：为了确定是否有终末期肺病患者发展移植前col（V）特异性细胞免疫，如果是这样，这种反应对PGD的影响。方法：使用跨体内迟发型超敏反应（TV-DTH）测定来评估55名等待肺移植的患者对col（V）的记忆T细胞反应。采用Pa-o2/Fi（o2）指数评价PGD。进行单变量风险因素分析以确定与PGD相关的变量。用col（V）或不相关抗原免疫的大鼠进行肺同种移植，以确定先前的抗col（V）免疫是否在不存在同种异体反应性的情况下触发PGD。测量和主要结果：我们发现，在等待肺移植的患者中，58.8%（10/17）的特发性肺纤维化患者和15.8%（6/38）的非特发性肺纤维化患者检测为col（V）DTH阳性。Col（V）反应活性由CD 4（+）T细胞和单核细胞介导，并依赖于IL-17、IL-1 β和肿瘤坏死因子（TNF）-α。在移植后6-72小时，col（V）反应性患者与无反应性患者的Pao（2）/Fio（2）指数显著受损。单变量危险因素分析仅确定术前TV-DTH to col（V）和缺血时间为PGD的预测因素。最后，在大鼠肺同种移植模型中，col（V）致敏导致Pa-o 2/Fi（o 2）显著降低，局部TNF-α和IL-1 β产生增加，以及与对照同种移植物相比中度至重度细支气管炎/血管炎。结论：数据表明，通过col（V）特异性Th-17记忆细胞激活先天免疫是肺移植后PGD的新途径。
Rationale: The pathogenesis of primary graft dysfunction (PGD), a serious complication of lung transplantation, is poorly understood. Human studies and rodent models have shown that Collagen type V (col[V]), stimulates IL-17-dependent cellular immunity after lung transplantation.Objectives: To determine whether patients with end-stage lung disease develop pretransplant col(V)-specific cellular immunity, and if so, the impact of this response on PGD.Methods: Trans-vivo delayed-type hypersensitivity (TV-DTH) assays were used to evaluate memory T-cell responses to col(V) in 55 patients awaiting lung transplantation. Pa-o2/Fi(o2) index data were used to assess PGD. Univariate risk factor analysis was performed to identify variables associated with PGD. Rats immunized with col(V) or irrelevant antigen underwent lung isografting to determine if prior anti-col(V) immunity triggers PGD in the absence of alloreactivity. Measurements and MainResults: We found that 58.8% (10/17) of patients with idiopathic pulmonary fibrosis, and 15.8% (6/38) of patients without idiopathic pulmonary fibrosis tested while on the wait list for a lung transplant were col(V) DTH positive. Col(V) re activity was CD4(+) T-cell and monocyte mediated, and dependent on IL-17, IL-1 beta, and tumor necrosis factor (TNF)-alpha. Pao(2)/Fio(2) indices were impaired significantly 6-72 hours after transplantation in col(V)-reactive versus nonreactive patients. Univariate risk factor analysis identified only preoperative TV-DTH to col(V) and ischemic time as predictors of PGD. Finally, in a rat lung isograft model, col(V) sensitization resulted in significantly lower Pa-o2/Fi(o2) increased local TNF-alpha and IL-1 beta production, and a moderate-to-severe bronchiolitis/vasculitis when compared with control isografts.Conclusions: The data suggest that activation of innate immunity by col(V)-specific Th-17 memory cells represents a novel pathway to PGD after lung transplantation..