Donor antigen-presenting cell-independent rejection of islet xenografts.

Donor antigen-presenting cell-independent rejection of islet xenografts.
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胰岛异种移植物的供体抗原呈递细胞独立排斥。

DOI:
10.1097/00007890-199511270-00018
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发表时间:
1995
期刊:
影响因子:
6.2
通讯作者:
Gill,RG
Gill,RG
中科院分区:
医学2区
文献类型:
--
作者:
Wolf,LA;Coulombe,M;Gill,RG

文献摘要

被引文献

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供体来源的抗原呈递细胞(APC)被认为是引发同种异体组织移植排斥反应的主要刺激物。然而,相对于同种异体T细胞的相应反应,APC刺激异种T细胞的能力通常不足。因此,供体型APC在异种移植排斥反应中的作用尚不清楚。我们使用一个和谐的物种组合(大鼠与小鼠),研究了供体型APC在触发胰岛异种移植排斥反应中的需求。尽管供体型APC的耗尽导致同种异体移植物的无限期存活,但异种大鼠胰岛APC的类似耗尽仅导致移植物的适度延长。此外,apc缺失的大鼠异种移植物通过CD8+ T细胞不依赖的机制被排斥,这是通过单克隆抗体治疗适当地消耗T细胞亚群来确定的。这与胰岛同种异体移植排斥反应对CD4+和CD8+ T细胞的依赖性形成对比。尽管体外实验表明,大鼠APC可以直接刺激小鼠T细胞,但在体内,异种移植物免疫似乎并不需要大鼠APC。我们得出结论,同种异体胰岛移植和异种胰岛移植排斥反应的机制在对供体APC的依赖和T细胞亚群在反应中的作用方面有所不同。
Donor-derived antigen-presenting cells (APC) are thought to serve as major stimulators for triggering the rejection of tissue allografts. However, the capacity of APC to stimulate xenogeneic T cells is generally deficient relative to the corresponding response from allogeneic T cells. For this reason, the contribution of donor-type APC to xenogeneic graft rejection remains unclear. Using a concordant species combination (rat to mouse), we examined the requirement for donor-type APC in triggering islet xenograft rejection. While the depletion of donor-type APC resulted in indefinite allograft survival, similar depletion of APC from xenogeneic rat islets resulted in only modest graft prolongation. Furthermore, APC-depleted rat xenografts were rejected by a CD8+ T cell-independent mechanism, as determined by appropriate depletion of T cell subsets through monoclonal antibody therapy. This contrasts with the dependence of islet allograft rejection on both CD4+ and CD8+ T cells. Although in vitro experiments show that rat APC can directly stimulate mouse T cells, rat APC do not appear to be required for xenograft immunity in vivo. We conclude that the mechanisms of islet allograft and xenograft rejection differ both in the dependence on donor-type APC and in the role of T cell subsets in the response.