TY - JOUR
T1 - Stimulation of host NKT cells by synthetic glycolipid regulates acute graft-versus-host disease by inducing Th2 polarization of donor T cells
AU - Hashimoto, Daigo
AU - Asakura, Shoji
AU - Miyake, Sachiko
AU - Yamamura, Takashi
AU - Van Kaer, Luc
AU - Liu, Chen
AU - Tanimoto, Mitsune
AU - Teshima, Takanori
PY - 2005/1/1
Y1 - 2005/1/1
N2 - 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 α-galactosylceramide (α-GalCer) to recipient mice on day O following allogeneic bone marrow transplantation promoted Th2 polarization of donor T cells and a dramatic reduction of serum TNF-α, a critical mediator of GVHD. A single injection of α-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 α-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.
AB - 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 α-galactosylceramide (α-GalCer) to recipient mice on day O following allogeneic bone marrow transplantation promoted Th2 polarization of donor T cells and a dramatic reduction of serum TNF-α, a critical mediator of GVHD. A single injection of α-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 α-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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U2 - 10.4049/jimmunol.174.1.551
DO - 10.4049/jimmunol.174.1.551
M3 - Article
C2 - 15611282
AN - SCOPUS:10844271455
VL - 174
SP - 551
EP - 556
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -