Intragraft gene expression profile associated with the induction of tolerance by allochimeric MHC I in the rat heart transplantation model.
Intragraft gene expression profile associated with the induction of tolerance by allochimeric MHC I in the rat heart transplantation model.
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移植物内基因表达谱与大鼠心脏移植模型中异源嵌合 MHC I 诱导耐受相关。
DOI：
10.1002/dvg.20574
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Ghobrial,RafikM
中科院分区：
文献类型：
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作者：
Lisik,Wojciech;Gong,Yongquan;Tejpal,Neelam;Skelton,ThomasS;Bremer,EricG;Kloc,Malgorzata;Ghobrial,RafikM
在受体类型重链上含有供体类型表位的MHC-I类同种异体嵌合蛋白可诱导大鼠异位心脏移植物无限期存活。分析同种异体心脏移植组织的基因表达谱。将含有供体型(Wistar Furth，WF；RT1u)免疫原性表位的突变肽[α1H1/u]-RT1Aa在移植时注入WF心脏急性脑梗塞患者体内，并口服环孢素A。使用Affymetrix Rate 230 2.0微阵列进行微阵列分析。异基因嵌合分子治疗导致与心肌结构完整性相关的基因上调，下调免疫反应的关键调节因子IL-1β，并下调与T细胞极性、运动性和扫描树突状细胞(DC)能力有关的有缺陷的6个同源基因伽马PAR6。提示同种异体分子的免疫抑制作用和/或同种异体移植耐受的建立依赖于心脏组织完整性相关基因的诱导，细胞因子途径的抑制(S)，以及T细胞迁移率及其DC扫描能力的损害。这些新的发现可能对抑制移植受者的慢性排斥反应具有重要的临床意义。创世纪48：8-19,2010。©2009威利-利斯，Inc.
The MHC class I allochimeric protein containing donor‐type epitopes on recipient‐type heavy chains induces indefinite survival of heterotopic cardiac allografts in rats. We analyzed gene expression profile of heart allograft tissue. Mutated peptide [α1h1/u]‐RT1.Aa that contains donor‐type (Wistar Furth, WF; RT1u) immunogenic epitopes displayed on recipient‐type (ACI, RT1a) was delivered into ACI recipients of WF hearts at the time of transplantation in addition to a 3 days course of oral cyclosporine. Microarray analysis was performed using Affymetrix Rat 230 2.0 Microarray. Allochimeric molecule treatment caused upregulation of genes involved in structural integrity of heart muscle, downregulation of IL‐1β a key modulator of the immune response, and downregulation of partitioning defective six homolog gamma PAR6, which is involved in T cell polarity, motility, and ability to scan dendritic cells (DC). These indicate that the immunosuppressive function of allochimeric molecule and/or the establishment of allograft tolerance depend on the induction of genes responsible for the heart tissue integrity, the suppression of cytokine pathway(s), and possibly the impairment of T cells mobility and their DC scanning ability. These novel findings may have important clinical implications for inhibition of chronic rejection in transplant recipients. genesis 48:8–19, 2010. © 2009 Wiley‐Liss, Inc.