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* Biopathological Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan;
Department of Immunology, National Institute of Neuroscience, Tokyo, Japan;
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232;
Department of Pathology, University of Florida College of Medicine, Gainesville, FL 32610; and
¶ Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan
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
-galactosylceramide (
-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-
, a critical mediator of GVHD. A single injection of
-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
-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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