Host-residual invariant NK T cells attenuate graft-versus-host immunity
Host-residual invariant NK T cells attenuate graft-versus-host immunity
复制标题
DOI：
10.4049/jimmunol.175.2.1320
复制
发表时间：
2005-07-15
影响因子：
4.4
通讯作者：
Chiba, S
中科院分区：
文献类型：
--
作者：
Haraguchi, K;Takahashi, T;Chiba, S
不变的NKT(iNKT)细胞具有不变的TCR-α链并且以CD1d限制的方式激活。它们被认为可以调节免疫反应，并在自身免疫、过敏、感染和肿瘤免疫中发挥重要作用。它们似乎还会影响造血干细胞移植后的免疫力。在这项研究中，我们使用 α-半乳糖神经酰胺、体外扩增的 NKT 细胞和缺乏 iNKT 细胞的 J α 18 敲除小鼠等材料，在 MHC 不匹配骨髓移植的小鼠模型中检查了 iNKT 细胞在移植物抗宿主病 (GVHD) 和移植物排斥中的作用。我们发现宿主残留的 iNKT 细胞构成效应细胞，在减轻 GVHD 严重程度方面发挥着至关重要的作用，并且这种减少与血清 Th2 细胞因子水平的延迟增加有关。有趣的是，我们还发现宿主残留的 iNKT 会导致植入延迟，并且在某些条件下会导致移植物排斥。这些结果表明宿主残留的 iNKT 细胞减弱移植物抗宿主免疫，而不是减弱宿主抗移植物免疫。
Invariant NK T (iNKT) cells have an invariant TCR-alpha chain and are activated in a CDld-restricted manner. They are thought to regulate immune responses and play important roles in autoimmunity, allergy, infection, and tumor immunity. They also appear to influence immunity after hemopoietic stem cell transplantation. In this study, we examined the role of iNKT cells in graft-vs-host disease (GVHD) and graft rejection in a mouse model of MHC-mismatched bone marrow transplantation, using materials including alpha-galactosylceramide, NKT cells expanded in vitro, and J alpha 18 knockout mice that lack iNKT cells. We found that host-residual iNKT cells constitute effector cells which play a crucial role in reducing the severity of GVHD, and that this reduction is associated with a delayed increase in serum Th2 cytokine levels. Interestingly, we also found that host-residual iNKT cause a delay in engraftment and, under certain conditions, graft rejection. These results indicate that host-residual iNKT cells attenuate graft-vs-host immunity rather than host-vs-graft immunity.