Teshima Takanori, Ordemann Rainer, Reddy Pavan, Gagin Svetlana, Liu Chen, Cooke Kenneth R, Ferrara James L M
Department of Internal Medicine, University of Michigan Cancer Center, Ann Arbor, Michigan, USA.
Nat Med. 2002 Jun;8(6):575-81. doi: 10.1038/nm0602-575.
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.
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）至关重要；因此，宿主靶上皮细胞上的同种异体抗原表达也被认为是组织损伤所必需的。我们在GvHD小鼠模型中使用骨髓嵌合体来验证这一假设，在该模型中，主要组织相容性复合体I类或II类同种异体抗原仅在APC上表达。我们发现，急性GvHD并不需要宿主靶上皮细胞上的同种异体抗原表达，并且肿瘤坏死因子-α和白细胞介素-1的中和作用可预防急性GvHD。这些结果尤其适用于CD4介导的GvHD，但至少部分也适用于CD8介导的GvHD。这些结果挑战了当前关于GvHD效应机制抗原特异性的范式，并证实了宿主APC和炎性细胞因子在急性GvHD中的核心作用。
