Stimulation of host NKT cells by synthetic glycolipid regulates acute graft-versus-host disease by inducing Th2 polarization of donor T cells
Stimulation of host NKT cells by synthetic glycolipid regulates acute graft-versus-host disease by inducing Th2 polarization of donor T cells
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DOI：
10.4049/jimmunol.174.1.551
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发表时间：
2005-01-01
影响因子：
4.4
通讯作者：
Teshima, T
中科院分区：
文献类型：
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作者：
Hashimoto, D;Asakura, S;Teshima, T
NKT 细胞是一种独特的免疫调节 T 细胞群，可产生大量细胞因子。我们研究了刺激宿主 NKT 细胞是否可以调节小鼠的急性移植物抗宿主病 (GVHD)。在同种异体骨髓移植后的第 0 天，向受体小鼠注射合成 NKT 细胞配体 α-半乳糖神经酰胺 (α-GalCer)，促进供体 T 细胞的 Th2 极化，并显着减少血清 TNF-α（GVHD 的关键介质）。向受体小鼠单次注射 α-GalCer 可显着降低 GVHD 的发病率和死亡率。然而，相同的治疗无法在NKT细胞缺陷型CD1d敲除(CDld(-/-))或IL-4(-/-)受体小鼠中或当STAT6(-/-)小鼠用作供体时提供针对GVHD的保护，这表明宿主NKT细胞、宿主IL-4的产生以及由供体T细胞介导的Th2细胞因子应答对α-GalCer针对GVHD的保护作用的关键作用。因此，通过给予NKT配体刺激宿主NKT细胞可以通过STAT6依赖性机制诱导供体T细胞的Th2极化来调节急性GVHD，并且可能代表预防急性GVHD的新策略。
NKT cells are a unique immunoregulatory T cell population that produces large amounts of cytokines. We have investigated whether stimulation of host NKT cells could modulate acute graft-vs-host disease (GVHD) in mice. Injection of the synthetic NKT cell ligand alpha-galactosylceramide (alpha-GalCer) to recipient mice on day 0 following allogeneic bone marrow transplantation promoted Th2 polarization of donor T cells and a dramatic reduction of serum TNF-alpha, a critical mediator of GVHD. A single injection of alpha-GalCer to recipient mice significantly reduced morbidity and mortality of GVHD. However, the same treatment was unable to confer protection against GVHD in NKT cell-deficient CD1d knockout (CDld(-/-)) or IL-4(-/-) recipient mice or when STAT6(-/-)mice were used as donors, indicating the critical role of host NKT cells, host production of IL-4, and Th2 cytokine responses mediated by donor T cells on the protective effects of alpha-GalCer against GVHD. Thus, stimulation of host NKT cells through administration of NKT ligand can regulate acute GVHD by inducing Th2 polarization of donor T cells via STAT6-dependent mechanisms and might represent a novel strategy for prevention of acute GVHD.