IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants
IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants
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DOI：
10.1172/jci28031
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发表时间：
2007-11-01
影响因子：
15.9
通讯作者：
Willkes, David S.
中科院分区：
文献类型：
--
作者：
Burlingham, William J.;Love, Robert B.;Willkes, David S.
闭塞性细支气管炎综合征（BOS）是肺移植失败的最常见原因。我们测试了细胞介导的对V型胶原蛋白的免疫[col（V）]在这一过程中的作用。在7年期间前瞻性监测PBMC对col（II）和col（V）的应答。来自肺移植受者的PBMC，而不是来自健康对照或肾移植后的col（V）反应性肺出血肾炎综合征患者的PBMC，经常是col（V）反应性的。Col（V）特异性应答依赖于CD 4（+）T细胞和单核细胞，并且需要IL-17和单核因子TNF-α和IL-1 β。强col（V）特异性应答与BOS的发生率和严重程度显著增加相关。急性排斥反应、HLA-DR错配移植和移植受者HLA特异性抗体的诱导与BOS的风险并不密切相关。这些数据表明，虽然同种异体免疫启动肺移植排斥，但由col（V）特异性Th 17细胞和单核细胞/巨噬细胞辅助细胞介导的新生自身免疫最终导致进行性气道闭塞。
Bronchiolitis obliterans syndrome (BOS), a process of fibro-obliterative occlusion of the small airways in the transplanted lung, is the most common cause of lung transplant failure. We tested the role of cell-mediated immunity to collagen type V [col(V)] in this process. PBMC responses to col(II) and col(V) were monitored prospectively over a 7-year period. PBMCs from lung transplant recipients, but not from healthy controls or col(V)-reactive Goodpasture's syndrome patients after renal transplant, were frequently col(V) reactive. Col(V)-specific responses were dependent on both CD4(+) T cells and monocytes and required both IL-17 and the monokines TNF-alpha and IL-1 beta. Strong col(V)-specific responses were associated with substantially increased incidence and severity of BOS. Incidences of acute rejection, HLA-DR mismatched transplants, and induction of HLA-specific antibodies in the transplant recipient were not as strongly associated with a risk of BOS. These data suggest that while alloinimunity initiates lung transplant rejection, de novo autoinummity mediated by col(V)-specific Th17 cells and monocyte/macrophage accessory cells ultimately causes progressive airway obliteration.