Lymphatic neoangiogenesis in human kidney transplants is associated with immunologically active lymphocytic infiltrates
Lymphatic neoangiogenesis in human kidney transplants is associated with immunologically active lymphocytic infiltrates
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DOI：
10.1097/01.asn.0000113316.52371.2e
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发表时间：
2004-03-01
影响因子：
13.6
通讯作者：
Raab, I
中科院分区：
文献类型：
--
作者：
Kerjaschki, D;Regele, HM;Raab, I
肾移植排斥反应是由富含淋巴细胞的炎症浸润攻击皮质小管和内皮细胞引起的。免疫抑制治疗减少浸润细胞的数量；然而，他们的退出路线尚不清楚。此处，使用淋巴管内皮标记蛋白足足蛋白抗体对人肾移植活检进行免疫组织化学分析，证明具有结节性单核浸润的移植物中的淋巴管密度比正常肾脏增加了 50 倍以上。结节性浸润不断与新形成的、表达Ki-67的淋巴管相关，并包含T和B淋巴细胞的全部库，以提供特异性细胞和体同种异体抗原免疫反应，包括Ki-67（+）CD4（+）和CD8（+）T淋巴细胞、S100（+）树突状细胞和Ki-67（+）CD20（+）B淋巴细胞和lambda-和表达κ链的浆细胞样细胞。结节浸润内的大量趋化因子受体CCR7(+)细胞似乎被次级淋巴趋化因子(SLC/CCL21)所吸引，次级淋巴趋化因子是由淋巴内皮细胞与podoplanin复合物产生和释放的。从这些结果推测，淋巴新生血管生成不仅有助于排斥浸润的输出，而且还参与维持肾移植中潜在有害的同种反应性免疫反应，并提供新的治疗靶点。
Renal transplant rejection is caused by a lymphocyterich inflammatory infiltrate that attacks cortical tubules and endothelial cells. immunosupressive therapy reduces the number of infiltrating cells; however, their exit routes are not known. Here a >50-fold increase of lymphatic vessel density over normal kidneys in grafts with nodular mononuclear infiltrates is demonstrated by immunohistochemistry on human remal transplant biopsie susing antibodies to the lymphatic enclothelial inarker protein podoplanin. Nodular infiltrates are constantly associated with newly formed, Ki-67-expressing lymphatic vessels and contain the entire repertoire of T and B lymphocytes to provide specific cellular and hurnoral alloantigenic immune responses, including Ki-67(+) CD4(+) and CD8(+) T lymphocytes, S100(+) dendritic cells, and Ki-67(+) CD20(+) B lymphocytes and lambda- and kappa-chain-expressing plasmacytoid cells. Numerous chemokine receptor CCR7(+) cells within the nodular infiltrates seemed to be attracted by secondary lymphatic chemokine (SLC/CCL21) that is produced and released by lymphatic enclothelial cells in a complex with podoplanin. From these results, it is speculated that lymphatic neoangiogenesis not only contributes to the export of the rejection infiltrate but also is involved in the maintenance of a potentially detrimental alloreactive immune response in renal transplants and provides a novel therapeutic target.