Acute graft-versus-host disease does not require alloantigen expression on host epithelium
Acute graft-versus-host disease does not require alloantigen expression on host epithelium
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DOI：
10.1038/nm0602-575
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发表时间：
2002-06-01
期刊：
影响因子：
82.9
通讯作者：
Ferrara, JLM
中科院分区：
文献类型：
--
作者：
Teshima, T;Ordemann, R;Ferrara, JLM
宿主抗原呈递细胞（APC）上的同种异体抗原表达对于引发移植物抗宿主病（GvHD）是必不可少的;因此，宿主靶上皮上的同种异体抗原表达也被认为是组织损伤所必需的。我们测试了这一假设在小鼠模型中的GvHD使用骨髓嵌合体，其中无论是主要组织相容性复合物I类或II类同种异体抗原只表达在APC。我们发现急性GvHD不需要宿主靶上皮细胞表达同种异体抗原，中和肿瘤坏死因子-α和白细胞介素-1可以预防急性GvHD。这些结果特别适用于CD 4介导的GvHD，但也至少部分适用于CD 8介导的GvHD。这些结果挑战了目前关于GvHD效应机制的抗原特异性的范式，并证实了宿主APC和炎性细胞因子在急性GvHD中的核心作用。
Alloantigen expression on host antigen-presenting cells (APCs) is essential to initiate graft-versus-host disease (GvHD); therefore, alloantigen expression on host target epithelium is also thought to be essential for tissue damage. We tested this hypothesis in mouse models of GvHD using bone-marrow chimeras in which either major histocompatibility complex class I or class II alloantigen was expressed only on APCs. We found that acute GvHD does not require alloantigen expression on host target epithelium and that neutralization of tumor necrosis factor-alpha and interleukin-1 prevents acute GvHD. These results pertain particularly to CD4-mediated GvHD but also apply, at least in part, to CD8-mediated GvHD. These results challenge current paradigms about the antigen specificity of GvHD effector mechanisms and confirm the central roles of both host APCs and inflammatory cytokines in acute GvHD.