T helper17 cells are sufficient but not necessary to induce acute graft-versus-host disease.
T helper17 cells are sufficient but not necessary to induce acute graft-versus-host disease.
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DOI：
10.1016/j.bbmt.2009.09.023
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发表时间：
2010-02
影响因子：
4.3
通讯作者：
Yu, Xue-Zhong
中科院分区：
文献类型：
--
作者：
Iclozan, Cristina;Yu, Yu;Liu, Chen;Liang, Yaming;Yi, Tangsheng;Anasetti, Claudio;Yu, Xue-Zhong
辅助性T细胞（Th）1被认为是引起移植物抗宿主病（GVHD）的主要原因，但近来这一观点受到质疑。Th 17细胞在介导自身免疫性疾病中起关键作用，但其在GVHD发病机制中的作用仍不清楚。在此，我们比较了体外产生的Th 1和Th 17细胞从C57 BL/6小鼠诱导GVHD致死照射BALB/c受体的能力。与未感染或Th 1对照相比，同种异体Th 17细胞在GVHD靶器官中具有上级扩增和浸润能力，这与其致病性增强相关。Th 17细胞在同基因受体中未引起病理学改变，表明抗原活化是其致病性所必需的。极化的Th 17细胞不能在体内维持其表型，因为它们在移植到异基因受体后产生显著量的干扰素（IFN）-γ;然而，IFN-γ不是Th 17细胞诱导的GVHD所必需的。此外，我们通过在临床相关的异基因骨髓移植（BMT）环境中使用多克隆非致敏CD 4 T细胞来评估Th 17细胞在GVHD中的发病机制。我们发现，通过靶向RORγt（Th 17特异性转录因子）单独破坏Th 17分化对GVHD的发展没有显著影响。我们的结论是，Th 17细胞是足够的，但不是必需的诱导GVHD。
T helper (Th)1 cells were considered responsible for the induction of graft-versus-host disease (GVHD), but recently the concept has been challenged. Th17 cells play a critical role in mediating autoimmune diseases, but their role in the pathogenesis of GVHD remains unclear. Herein we compare the ability of in vitro generated Th1 and Th17 cells from C57BL/6 mice to induce GVHD in lethally irradiated BALB/c recipients. Allogeneic Th17 cells had superior expansion and infiltration capabilities in GVHD target organs, which correlated with their increased pathogenicity when compared with naïve or Th1 controls. Th17 cells caused no pathology in the syngeneic recipients, indicating that antigen-activation was required for their pathogenicity. Polarized Th17 cells could not maintain their phenotype in vivo as they produced a significant amount of interferon (IFN)-γ after being transplanted into allogeneic recipients; however, IFN-γ was not required for Th17 cell-induced GVHD. Further, we evaluated the pathogenesis of Th17 cells in GVHD by using polyclonal nonprimed CD4 T cells in a clinically relevant allogeneic bone marrow transplantation (BMT) setting. We found that disruption of Th17-differentiation alone by targeting RORγt (Th17-specific transcription factor) had no significant effect on GVHD development. We conclude that Th17 cells are sufficient but not necessary to induce GVHD.
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