Characterisation of Tertiary Lymphoid Organs in Explanted Rejected Donor Kidneys
Characterisation of Tertiary Lymphoid Organs in Explanted Rejected Donor Kidneys
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DOI：
10.3109/08820139.2015.1085394
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发表时间：
2016-01
影响因子：
2.8
通讯作者：
Xiao-guang Xu;Yong Han;Qiang Wang;M. Cai;Y. Qian;Xinying Wang;Haiyan Huang;Liang Xu;L. Xiao;B. Shi
中科院分区：
文献类型：
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作者：
Xiao-guang Xu;Yong Han;Qiang Wang;M. Cai;Y. Qian;Xinying Wang;Haiyan Huang;Liang Xu;L. Xiao;B. Shi
摘要目的：第三淋巴器官（TLO）已在器官同种异体移植物中得到描述，但它们是否促进破坏性或有益的同种免疫反应仍存在争议。本研究旨在表征人类慢性排斥肾同种异体移植物中 TLO 的分布并探讨其功能。方法：对29例慢性排斥和12例急性排斥同种异体移植肾进行免疫组织化学分析。免疫组化检测TLO、T细胞、滤泡树突状细胞、B细胞、滤泡调节性T（Tfr）细胞的分布，以及Ki67、外周淋巴结寻址蛋白（PNAd）、足足蛋白、AID、IL-17、IL-21、IL-10、C4d的表达。评估淋巴新生与 IL-17、IL-21、C4d、podoplanin、IL-10 和 Foxp3 表达之间的相关性。此外，还比较了含有或缺乏 TLO 的同种异体移植物的移植功能持续时间。结果：27.6%的慢性排斥肾移植物中检测到TLO，但它们很少有生发中心。淋巴新生与CXCR5表达负相关，与IL-17表达几乎完全相关。那些带有 TLO 的移植物的平均功能时间为 5.98 年，而那些没有 TLO 的移植物的寿命只有大约一半，平均为 2.91 年。然而，在含有 TLO 的移植物中，Foxp3+ 细胞相对少于没有 TLO 的移植物。无论 TLO 是否存在，移植物中 Foxp3+CXCR5+ Tfr 细胞和 IL-10+ 细胞都很罕见。结论：慢性排斥同种异体肾移植物中的 TLO 可能是与移植持续时间相关的炎症过程的附带现象。
ABSTRACT Purpose: Tertiary lymphoid organs (TLOs) have been described within organ allografts, but whether they promote destructive or beneficial alloimmune responses remains controversial. This study aimed to characterize TLO distribution in human chronically rejected renal allografts and to explore their functions. Methods: A total of 29 explanted chronically rejected and 12 acutely rejected renal allografts were analyzed by immunohistochemistry. The distribution of TLOs, T cells, follicular dendritic cells, B cells, and follicular regulatory T (Tfr) cells, as well as Ki67, peripheral lymph node addressin (PNAd), podoplanin, AID, IL-17, IL-21, IL-10, and C4d expression were detected by immunohistochemistry. Correlations between lymphoid neogenesis and the expression of IL-17, IL-21, C4d, podoplanin, IL-10, and Foxp3 were evaluated. In addition, the duration of graft function was compared between allografts that harbored or lacked TLOs. Results: TLOs were detected in 27.6% of chronically rejected renal grafts, but they rarely had germinal centers. Lymphoid neogenesis negatively correlated with CXCR5 expression, and almost completely correlated with IL-17 expression. Those grafts that harbored a TLO functioned for an average of 5.98 years and those without a TLO lasted only about half as long with an average of 2.91 years. However, in grafts that harbored a TLO, Foxp3+ cells were comparitively less than those without a TLO. Foxp3+CXCR5+ Tfr cells and IL-10+ cells were rare in grafts, irrespective of the presence of a TLO. Conclusion: TLOs in chronically rejected kidney allografts may be an epiphenomenon of the inflammatory process that is related to graft duration.