T cells in islet-like cell cluster xenograft rejection - A study in the pig-to-mouse model
T cells in islet-like cell cluster xenograft rejection - A study in the pig-to-mouse model
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DOI：
10.1097/00007890-199808270-00004
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发表时间：
1998-08-27
期刊：
影响因子：
6.2
通讯作者：
Korsgren, O
中科院分区：
文献类型：
--
作者：
Benda, B;Sandberg, JO;Korsgren, O
背景本研究的目的是评估T细胞参与的性质，并推测，胎儿猪胰岛样细胞簇（ICC）异种移植排斥反应的关键，方法。在正常小鼠和T细胞受体（TCR）-β-、TCR-δ-或TCR-β X δ-缺陷小鼠的肾被膜下移植胎猪ICC。穿孔蛋白或颗粒酶B（GraB）缺陷型小鼠用于进一步表征T细胞依赖性途径。为了评价T细胞在巨噬细胞活化过程中的作用，用重组小鼠肿瘤坏死因子（TNF）-α处理TCR-β x δ突变体。此外，移植有猪ICC的正常小鼠用MDL 201，449 A处理，MDL 201，449 A是TNF-α的新型转录抑制剂，结果。在正常小鼠中，大多数浸润细胞是表达巨噬细胞特异性表型标志物F4/80的大的巨噬细胞样细胞，发现CD 3（+）T淋巴细胞主要积聚在ICC异种移植物的外周部分，TCR-β突变体和TCR-β x δ突变体没有表现出异种移植物排斥的迹象，而TCR-δ突变体和穿孔素和GraB缺陷动物排斥ICC异种移植物。移植后高剂量重组小鼠TNF-α治疗TCR-β x δ突变体不会导致胎猪ICC异种移植排斥反应。然而，在异种移植物区域内观察到F4/80（+）和Mac-1（+）细胞的数量略有增加。类似地，尽管没有发现移植物存活延长，但在用MDL 201，449 A处理的小鼠中观察到CD 4（+）T细胞数量减少。结论，在猪-小鼠模型中，胎猪ICC异种移植排斥完全依赖于携带TCR-α β链的T细胞。此外，穿孔素或GraB的缺乏对排斥过程没有影响，表明异种特异性溶细胞性T细胞的重要性较小。即使TNF-α对ICC异种移植物排斥的发展过程很重要，其他细胞因子，即，干扰素-γ可能有效地替代TNF-α的缺乏。
Background. The aim of the present study was to evaluate the nature of T cells involved in and, presumably, critical to fetal porcine islet-like cell cluster (ICC) xenograft rejection,Methods. Normal mice and T cell receptor (TCR)-beta-, TCR-delta-, or TCR-beta x delta-deficient mice were transplanted with fetal porcine ICC under the kidney capsule. Perforin- or granzyme B (GraB)-deficient mice were used to further characterize T cell-dependent pathways, For evaluation of the role of T cells in the activation process of macrophages, TCR-beta x delta mutants were treated with recombinant mouse tumor necrosis factor (TNF)-alpha. In addition, normal mice transplanted with porcine ICC were treated with MDL 201,449A, a novel transcriptional inhibitor of TNF-alpha,Results. In normal mice, the majority of the infiltrating cells were large, macrophage-like cells expressing the macrophage specific phenotype marker F4/80, CD3(+) T lymphocytes were found to be mainly accumulated in the peripheral parts of the ICC xenograft, TCR-beta mutants and TCR-beta x delta mutants exhibited no signs of xenograft rejection, whereas TCR-delta mutants and perforin- and GraB-deficient animals rejected the ICC xenograft. Posttransplant high-dose recombinant mouse TNF-alpha-treatment of TCR-beta x delta mutants did not result in fetal porcine ICC xenograft rejection. However, a somewhat increased amount of F4/80(+) and Mac-1(+) cells was observed within the xenograft area. Similarly, although graft survival was not found to be prolonged, reduced numbers of CD4(+) T cells were observed in mice treated with MDL 201,449A,Conclusions, In the pig-to-mouse model, fetal porcine ICC xenograft rejection is exclusively dependent on T cells bearing TCR-alpha beta chains. In addition, the absence of perforin or GraB has no influence on the rejection process, suggesting that xenospecific cytolytic T cells are of minor importance, Even if TNF-alpha is of importance to the developing process of ICC xenograft rejection, other cytokines, i.e., interferon-gamma, might efficiently substitute for the lack of TNF-alpha.