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. 2005 Jan 1;174(1):551-6.
doi: 10.4049/jimmunol.174.1.551.

Stimulation of host NKT cells by synthetic glycolipid regulates acute graft-versus-host disease by inducing Th2 polarization of donor T cells

Daigo Hashimoto  1 , Shoji Asakura, Sachiko Miyake, Takashi Yamamura, Luc Van Kaer, Chen Liu, Mitsune Tanimoto, Takanori Teshima
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Stimulation of host NKT cells by synthetic glycolipid regulates acute graft-versus-host disease by inducing Th2 polarization of donor T cells

Daigo Hashimoto et al. J Immunol. .

Abstract (VSports app下载)

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 VSports手机版. 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 (CD1d(-/-)) 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. .

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