CD8+ T cells contribute to the development of transplant arteriosclerosis despite CD154 blockade
CD8+ T cells contribute to the development of transplant arteriosclerosis despite CD154 blockade
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DOI：
10.1097/00007890-200006270-00022
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发表时间：
2000-06-27
期刊：
影响因子：
6.2
通讯作者：
Wood, KJ
中科院分区：
文献类型：
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作者：
Ensminger, SM;Witzke, O;Wood, KJ
背景资料。CD40-CD154受体-配体对通过介导内皮细胞、抗原提呈细胞和T细胞的激活在同种异体移植排斥反应中起关键作用。在许多实验模型中，阻断这种相互作用可防止移植物急性排斥反应，并导致移植物存活时间延长，但在大多数情况下，由于移植物动脉硬化的发展，移植物的无限期存活无法实现。在这项研究中，我们使用了一种移植动脉硬化的模型来研究CD154阻断对CD4(+)和CD8(+)T细胞是否有不同的影响。方法将BALB/c(H2(D))移植物移植到C57BL/6(H2(B))受体，在CD8(+)T细胞去除或不存在的情况下，用抗CD154单抗处理。移植后第30天进行组织学和形态计量学检查。仅联合应用抗CD154和抗CDS单抗可显著减少内膜增殖(33+/-10%vs.67+/-14%；未处理对照组)。单独使用任何一种抗体都不会产生这种效果。胸腺切除并不改变任何治疗组观察到的内膜增生程度。我们的数据提供了直接证据，表明CD8(+)T细胞没有被CD154阻断有效地靶向，并且CD154阻断后出现的移植动脉硬化不是由于最近胸腺移植物T细胞造成的。
Background. The CD40-CD154 receptor-ligand pair plays a critical role in allograft rejection by mediating the activation of endothelial cells, antigen-presenting cells, and T cells. Blockade of this interaction prevents acute allograft rejection and leads to prolonged allograft survival in numerous experimental models, but in most cases indefinite graft survival is not achieved due to evolving transplant arteriosclerosis. In this study, we have used a model of transplant arteriosclerosis to investigate whether CD4(+) and CD8(+) T cells are differentially affected by CD154 blockade.Methods, BALB/c (H2(d)) aortic grafts were transplanted into C57BL/6 (H2(b)) recipients treated with anti-CD154 monoclonal antibody in the presence or absence of CD8(+) T-cell depletion. Histology and morphometric measurements were performed on day 30 after transplantation.Results. Only combined treatment with anti-CD154 and anti-CDS monoclonal antibodies resulted in a significant reduction of intimal proliferation (33+/-10% vs. 67+/-14%; untreated control). Administration of either antibody alone did not produce this effect. Thymectomy did not alter the degree of intimal proliferation observed in any of the treatment groups.Conclusions. Our data provide direct evidence that CD8(+) T cells are not targeted effectively by CD154 blockade and that the transplant arteriosclerosis seen after CD154 blockade is not due to recent thymic emigrant T cells.