The Role of Intrapulmonary De Novo Lymphoid Tissue in Obliterative Bronchiolitis after Lung Transplantation
The Role of Intrapulmonary De Novo Lymphoid Tissue in Obliterative Bronchiolitis after Lung Transplantation
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DOI：
10.4049/jimmunol.0803606
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发表时间：
2009-06-01
影响因子：
4.4
通讯作者：
Keshavjee, Shaf
中科院分区：
文献类型：
--
作者：
Sato, Masaaki;Hirayama, Shin;Keshavjee, Shaf
肺移植后的慢性排斥反应表现为闭塞性细支气管炎（OB）。淋巴组织的新生（淋巴新生）的发育可能有助于小气道的局部免疫反应。与正常肺相比，13 名发生 OB 的肺移植受者的肺组织表现出大量淋巴组织特有的小型气道相关外周淋巴结地址阳性 (PNAd(+)) 高内皮微静脉 (HEV) (p < 0.001)。与“非活动性”OB 相比，HEV 在淋巴细胞性细支气管炎和淋巴细胞浸润的“活动性”OB 病变中最为丰富。淋巴细胞性细支气管炎和活动性 OB 中的 T 细胞主要为 CD45RO(+)CCR7(-) 效应记忆表型。同种异体气管肺内移植（布朗挪威（BN）至刘易斯）后，在大鼠肺中也观察到类似的淋巴组织，但同种移植后则没有。随后将含有 BN 气管的受体 Lewis 肺原位移植到 F-1 (Lewis x BN) 大鼠中，证明了 Lewis 衍生 T 细胞在肺中的稳定归巢及其针对次级肺内 BN 气管的 Ag 特异性效应器功能。总之，我们发现肺部的新生淋巴组织由效应记忆 T 细胞和 HEV 组成，但缺乏明确的 T 细胞和 B 细胞区域。这种从头淋巴组织可能在肺移植后的慢性局部免疫反应中发挥关键作用。免疫学杂志，2009，182：7307-7316。
Chronic rejection after lung transplantation is manifested as obliterative bronchiolitis (OB). The development of de novo lymphoid tissue (lymphoid neogenesis) may contribute to local immune responses in small airways. Compared with normal lungs, the lung tissue of 13 lung transplant recipients who developed OB demonstrated a significantly larger number of small, airway-associated, peripheral node addressin-positive (PNAd(+)) high endothelial venules (HEVs) unique to lymphoid tissue (p < 0.001). HEVs were most abundant in lesions of lymphocytic bronchiolitis and "active" OB infiltrated by lymphocytes compared with those of "inactive" OB. T cells in lymphocytic bronchiolitis and active OB were predominantly of the CD45RO(+)CCR7(-) effector memory phenotype. Similar lymphoid tissue was also observed in the rat lung after intrapulmonary transplantation of allograft trachea (Brown Norway (BN) to Lewis), but not after isograft transplantation. Subsequent orthotopic transplantation of the recipient Lewis lung containing a BN trachea into an F-1 (Lewis x BN) rat demonstrated stable homing of Lewis-derived T cells in the lung and their Ag-specific effector function against the secondary intrapulmonary BN trachea. In conclusion, we found de novo lymphoid tissue in the lung composed of effector memory T cells and HEVs but lacking delineated T cell and B cell zones. This de novo lymphoid tissue may play a critical role in chronic local immune responses after lung transplantation. The Journal of Immunology, 2009, 182: 7307-7316.