Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 551-556 |
| Number of pages | 6 |
| Journal | Journal of Immunology |
| Volume | 174 |
| Issue number | 1 |
| Publication status | Published - Jan 1 2005 |
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ASJC Scopus subject areas
- Immunology
Cite this
Stimulation of host NKT cells by synthetic glycolipid regulates acute graft-versus-host disease by inducing Th2 polarization of donor T cells. / Hashimoto, Daigo; Asakura, Shoji; Miyake, Sachiko; Yamamura, Takashi; Van Kaer, Luc; Liu, Chen; Tanimoto, Mitsune; Teshima, Takanori.
In: Journal of Immunology, Vol. 174, No. 1, 01.01.2005, p. 551-556.Research output: Contribution to journal › Article
}
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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UR - http://www.scopus.com/inward/citedby.url?scp=10844271455&partnerID=8YFLogxK
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 -