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

Hashimoto D, Asakura S, Miyake S, Yamamura T, Van Kaer L, Liu C, Tanimoto M, Teshima T
J Immunol. 2005 174 (1): 551-6

PMID: 15611282 · DOI:10.4049/jimmunol.174.1.551

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 (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.

MeSH Terms (18)

Animals Antigens, CD1 Antigens, CD1d Bone Marrow Transplantation Enzyme-Linked Immunosorbent Assay Female Flow Cytometry Galactosylceramides Glycolipids Graft vs Host Disease Mice Mice, Knockout STAT6 Transcription Factor T-Lymphocytes T-Lymphocyte Subsets Th2 Cells Trans-Activators Tumor Necrosis Factor-alpha

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