Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease
Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease
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DOI：
10.1182/blood-2009-05-219402
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发表时间：
2009-10-01
期刊：
影响因子：
20.3
通讯作者：
Zeng, Defu
中科院分区：
文献类型：
--
作者：
Yi, Tangsheng;Chen, Ying;Zeng, Defu
在急性移植物抗宿主病（GVHD）中，初始供者CD 4（+）T细胞识别宿主抗原呈递细胞上的同种异体抗原并分化为辅助性T细胞（Th）亚群（Th 1、Th 2和Th 17细胞），但Th亚群在GVHD发病机制中的作用尚不完全清楚。本文报道了在C57 BL/6供体与BALB/c受体MHC不匹配的模型中，WT供体的CD 4（+）T细胞主要分化为Th 1细胞，并优先介导肠道和肝脏的GVHD组织损伤。然而，干扰素-γ的缺失在CD 4（+）T细胞中IL-4和IFN-γ的缺乏导致Th 2和Th 17分化增强，并加重肺和皮肤中的组织损伤; IFN-γ和IL-17的缺乏导致Th 2分化和特发性肺炎的进一步增强。Th 1、Th 2和Th 17细胞介导的组织特异性GVHD部分与其趋化因子受体差异表达介导的组织特异性迁移有关。此外，IFN-γ诱导的B7-H1的组织表达的缺乏在增加Th 2介导的特发性肺炎中起关键作用。这些结果表明，供体CD 4（+）T细胞可以快速分化为Th 1，Th 2和Th 17细胞，介导器官特异性GVHD。（血。2009; 114：3101-3112）
In acute graft-versus-host disease (GVHD), naive donor CD4(+) T cells recognize alloantigens on host antigen-presenting cells and differentiate into T helper (Th) subsets (Th1, Th2, and Th17 cells), but the role of Th subsets in GVHD pathogenesis is incompletely characterized. Here we report that, in an MHC-mismatched model of C57BL/6 donor to BALB/c recipient, WT donor CD4(+) T cells predominantly differentiated into Th1 cells and preferentially mediated GVHD tissue dam-age in gut and liver. However, absence of interferon-gamma (IFN-gamma) in CD4(+) T cells resulted in augmented Th2 and Th17 differentiation and exacerbated tissue damage in lung and skin; absence of both IL-4 and IFN-gamma resulted in augmented Th17 differentiation and preferential, although not exclusive, tissue damage in skin; and absence of both IFN-gamma and IL-17 led to further augmentation of Th2 differentiation and idiopathic pneumonia. The tissue-specific GVHD mediated by Th1, Th2, and Th17 cells was in part associated with their tissue-specific migration mediated by differential expression of chemokine receptors. Furthermore, lack of tissue expression of the IFN-gamma -inducible B7-H1 played a critical role in augmenting the Th2-mediated idiopathic pneumonia. These results indicate donor CD4(+) T cells can reciprocally differentiate into Th1, Th2, and Th17 cells that mediate organ-specific GVHD. (Blood. 2009; 114: 3101-3112)