Second-set rejection of mouse liver allografts is dependent on radiation-sensitive nonparenchymal cells of graft bone marrow origin
Second-set rejection of mouse liver allografts is dependent on radiation-sensitive nonparenchymal cells of graft bone marrow origin
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DOI：
10.1097/00007890-199604270-00019
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发表时间：
1996-04-27
期刊：
影响因子：
6.2
通讯作者：
Qian, SG
中科院分区：
文献类型：
--
作者：
Fu, FM;Thai, NL;Qian, SG
从B10(H2(B))或BALB/c(H2(D))小鼠原位移植到C3H(H2(K))小鼠的肝脏在没有宿主免疫抑制的情况下被自发接受。然而，在肝移植前两周通过皮肤移植可以诱导对供者的预敏性，从而在4-5天内导致二次置换性或“加速”肝移植排斥反应。在本研究中，通过供体全身照射和供体B10肝非实质细胞(NPC)以第三方(BALB/c)或受体株(C3H)骨髓替换的方法，检测了肝脏非实质细胞(NPC)在二次集排斥反应中的作用。肝移植前单纯照射正常B10供者(9.5GY)可显著延长预敏CSII受者的移植物存活时间。骨髓移植(BMT)后3个月，将表达第三方或受体单倍型的嵌合肝脏原位移植到未经修饰的C3H受体体内。与正常或同基因重组的B10供者的肝脏相比，移植物存活时间显著延长。C3R小鼠对肝实质(B10)和第三方NPC(BALB/c)上表达的同种异体抗原预敏后，通过同时移植每个供体品系的皮肤，嵌合(BALB/c->；B10)小鼠的嵌合肝脏的存活时间也明显延长。移植后4d检测移植物细胞因子基因表达谱显示，与同基因重组供者相比，供者被第三方或受体BM来源的细胞株替代与IL-2和干扰素-γ的表达降低有关。然而，IL-10转录本没有受到显著影响，这一结果与辐射敏感的供体特异性鼻咽癌在预敏宿主的二次肝排斥反应中的关键作用是一致的。在这个过程中，合格的供体-鼻咽癌菌株似乎增强了负责第二集排斥反应的预置T细胞的活性。
Livers are accepted spontaneously when transplanted orthotopically from B10 (H2(b)) or BALB/c (H2(d)) to C3H (H2(k)) mice without host immunosuppression. Presensitization to donor can, however, be induced by skin grafting two weeks prior to liver transplantation, resulting in second-set or ''accelerated'' liver graft rejection, within 4-5 days. In this study, the role of liver nonparenchymal cells (NPC) in second-set rejection was tested by donor whole-body irradiation and replacement of donor B10 liver NPC with those of either third-party (BALB/c) or recipient strain (C3H) bone marrow. Irradiation alone (9.5 Gy) of normal B10 donors before liver transplantation significantly prolonged graft survival in presensitized CSII recipients. Three months after bone marrow transplantation (BMT), chimeric Livers expressing third-party or recipient haplotype, were transplanted orthotopically into unmodified C3H recipients. Graft survival was prolonged significantly compared with livers from normal or syngeneically reconstituted B10 donors. Prolonged survival of chimeric (BALB/c->B10) livers was also evident in C3R mice presensitized to alloantigens expressed on both the liver parenchymal (B10) and third-party NPC (BALB/c) by simultaneous grafting of skin from each donor strain. Determination of graft cytokine mRNA profiles 4 days posttransplant showed that replacement of donor with third-party or recipient strain BM-derived cells was associated with reduced expression of IL-2 and IFN-gamma mRNA compared with that in grafts from syngeneically reconstituted donors. IL-10 transcripts, however, were not significantly affected, The results are consistent with a key role of radiation-sensitive, donor-specific NPC of bone marrow origin in second-set liver rejection in presensitized hosts. In this process, competent donor-strain NPC appear to augment the activity of primed T cells responsible for the second-set rejection.