Immunodulation of intestinal transplantation: antilymphocyte serum donor pretreatment vs. ex vivo graft irradiation.
Immunodulation of intestinal transplantation: antilymphocyte serum donor pretreatment vs. ex vivo graft irradiation.
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肠移植的免疫调节：抗淋巴细胞血清供体预处理与离体移植物辐射。
DOI：
10.1016/s0041-1345(02)02731-8
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发表时间：
2002
影响因子：
0.9
通讯作者：
Murase,N
中科院分区：
文献类型：
--
作者：
Nakao,A;Nalesnik,MA;Azhipa,O;Ishikawa,T;Abu-Elmagd,K;Starzl,TE;Murase,N
方法在Brown Norway（BN，RT 1 n）和刘易斯（LEW，RT 1 l）大鼠品系组合中进行原位SITx，使用短期他克莫司治疗（1.0 mg/kg/d，0 - 13，20，27天，IM）。研究了三组受者：（1）对照组，（2）供者ALS预处理（1.0 mL/d，IP）3d+供者BM输注（第0天2.5× 10 8个细胞），（3）离体同种异体移植物照射（10戈伊）+供者BM输注。所有受试者随访150天。通过流式细胞术研究嵌合体的水平和谱系。RNA酶保护试验（RPA）检测细胞因子mRNA水平。在SITx后7天内，第1组中受体脾脏和血液中供体细胞的数量显著高于免疫调节的第2组和第3组受体（表1）。第2组宿主中供体细胞的减少主要由αβTCR+细胞的消耗引起，而供体B细胞的数量保持不变（数据未显示）。相反，在第3组中，供体细胞的所有谱系均被消除，导致低水平的嵌合。移植肠系膜淋巴结（MLN）中淋巴细胞的分析显示，与组1相比，免疫调节组2和3中供体细胞被受体淋巴细胞迅速替代。免疫调节与离体移植物照射导致更快速的细胞更换比ALS供体预处理。SITx后3天，组1中MLN中供体细胞的百分比为50.5%，而组2和组3分别为20.8%和2.5%。SITx后早期（第1天至第7天），第1组受体脾脏和移植MLN中Th 1型细胞因子（IL-2和γ-IFN）的mRNA水平升高;然而，第2组和第3组中这些细胞因子显著下调。第150天同种异体移植物的组织学分析显示，第1组出现慢性排斥反应（淋巴耗竭、派尔集合淋巴结和MLN纤维化变化以及动脉炎）。在免疫调节组2和3同种异体移植物中，这些变化被完全阻止。
METHODSOrthotopic SITx was performed in Brown Norway (BN, RT1 n) to Lewis (LEW, RT1 l) rat strain combination using a short course of tacrolimus treatment (1.0 mg/kg/d, days 0 to 13, 20, and 27, IM). Three groups of recipients were studied:(1) controls without immunomodulation,(2) donor ALS pretreatment for 3 days (1.0 mL/d, IP) plus donor BM infusion (2.5× 10 8 cells on day 0), and (3) ex vivo allograft irradiation (10 Gy) plus donor BM infusion. All recipients were followed for 150 days. Levels and lineages of chimerism were studied by flow cytometry. Cytokine mRNA levels were analyzed by RNase protection assay (RPA).RESULTSAll recipients in this study survived for> 150 days. The numbers of donor cells in recipient spleen and blood within 7 days after SITx were significantly greater among Group 1 than immunomodulated Group 2 and 3 recipients (Table 1). The decrease in donor cells among Group 2 hosts was mainly caused by the depletion of αβTCR+ cells, while the number of donor B cells was maintained (data not shown). In contrast, all lineages of donor cells were eliminated in Group 3, resulting in a low level of chimerism. Analysis of lymphocytes in graft mesenteric lymph nodes (MLN) showed prompt replacement of donor cells with recipient lymphocytes in immunomodulated Group 2 and 3 compared with Group 1. Immunomodulation with ex vivo graft irradiation resulted in a more rapid replacement of cells than ALS donor pretreatment. The percentage of donor cells in MLN 3 days after SITx was 50.5% in Group 1, whereas it was 20.8% and 2.5% for Group 2 and 3, respectively. mRNA levels for Th1-type cytokines (IL-2 and γ-IFN) were increased in spleen and graft MLN of Group 1 recipients early after SITx (day 1 to 7); however, these cytokines were significantly down-regulated in Group 2 and 3. Histopathological analysis of allografts at day 150 revealed the development of chronic rejection (lymphoid depletion, fibrotic changes of Peyer’s patches and MLN, and existence of arteritis) in Group 1. These changes were completely prevented in immunomodulated Group 2 and 3 allografts.