Predominant expression of Th2 cytokines and interferon-gamma in xenogeneic cardiac grafts undergoing acute vascular rejection.
Predominant expression of Th2 cytokines and interferon-gamma in xenogeneic cardiac grafts undergoing acute vascular rejection.
复制标题
经历急性血管排斥反应的异种心脏移植物中 Th2 细胞因子和干扰素-γ 的主要表达。
DOI：
10.1097/01.tp.0000052594.83318.68
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Shirwan,Haval
中科院分区：
文献类型：
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作者：
Singh,NarendraP;Guo,Luping;Mhoyan,Anna;Shirwan,Haval
Th 1应答在急性同种异体移植排斥反应中发挥作用，而Th 2应答则与同种异体移植物的保护有关。与同种异体移植物不同，实体器官异种移植物的细胞因子反应模式一直是有限研究的主题。我们研究了移植物内细胞因子的表达在一个和谐的心脏异种移植模型（大鼠到小鼠），以测试如果一个特定的细胞因子的配置文件占主导地位。方法。腹腔内心脏移植使用C57 BL/10小鼠作为受体的PVG。R8大鼠心脏。同基因移植物（C57 BL/10至C75 BL/10）作为对照。采用逆转录聚合酶链反应（RT-PCR）技术对移植后不同时间的心脏移植物进行组织学和移植物内细胞因子表达的分析。结果：该模型中的移植物被排斥，平均存活时间为7±1天，并显示出广泛的急性血管排斥证据，包括心肌结构的整体扭曲，细胞浸润减少，间质出血伴心肌细胞坏死血栓形成，以及嗜中性粒细胞和淋巴细胞浸润血管壁的血管炎。异种心脏移植物主要表达Th 2细胞因子、白细胞介素（IL）-4、IL-10和转化生长因子-β，具有不同的动力学。IL-10在移植后第1天可检测到，并在移植后第6天达到其表达高峰。IL-4在移植后第1天和第3天表现出最小的和不可检测的表达，并且在移植后第6天表现出显著的表达。转化生长因子-β在所有检查日均中度表达。IFN-γ是一种Th 1细胞因子，其表达对异种移植物具有特异性，并在移植后3 ~ 6天逐渐增加。与此形成鲜明对比的是，IL-2显示完全缺乏表达。结论：我们的数据表明，在发生急性血管排斥反应的异种心脏移植物中，Th 2细胞因子和IFN-γ的表达占主导地位。Th 2细胞因子可能通过调节体液反应促进急性血管排斥反应，IFN-γ可能延迟但不能阻止这种反应。
Background.The Th1 response has been shown to play a role in acute allograft rejection, whereas the Th2 response has been implicated in the protection of allografts. Unlike allografts, the pattern of cytokines in response to solid-organ xenografts has been the subject of limited studies. We investigated intragraft cytokine expression in a concordant cardiac xenograft model (rat-to-mouse) to test if a particular cytokine profile predominates.Methods.Intra-abdominal cardiac transplantation was performed using C57BL/10 mice as recipients of PVG. R8 rat hearts. Syngeneic grafts (C57BL/10-to-C75BL/10) served as controls. Cardiac grafts harvested on various days posttransplantation were analyzed for histology and intragraft cytokine expression using reverse-transcriptase polymerase chain reaction.Results.The grafts in this model were rejected with a mean survival time of 7±1 days and showed extensive evidence of acute vascular rejection, consisting of global distortion of myocardial architecture, fewer cellular infiltrates, interstitial hemorrhage with myocyte necrosis thrombosis, and vasculitis with neutrophils and lymphocytes infiltrating vessel walls. Cardiac xenografts predominantly expressed Th2 cytokines, interleukin (IL)-4, IL-10, and transforming growth factor-β with various kinetics. IL-10 was detectable on day 1 and reached its peak level of expression on day 6 posttransplantation. IL-4 showed minimal and undetectable expression on days 1 and 3 and significant expression on day 6 posttransplantation. Transforming growth factor-β was expressed moderately on all days examined. The expression of interferon (IFN)-γ, a Th1 cytokine, was specific to xenografts and showed a gradual increase from days 3 to 6 posttransplantation. In marked contrast, IL-2 showed complete lack of expression.Conclusions.Our data demonstrate predominant expression of Th2 cytokines and IFN-γ in cardiac xenografts undergoing acute vascular rejection. The Th2 cytokines may promote acute vascular rejection by regulating the humoral response, and IFN-γ may delay, but not prevent, this response.