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

Daigo Hashimoto, Shoji Asakura, Sachiko Miyake, Takashi Yamamura, Luc Van Kaer, Chen Liu, Mitsune Tanimoto, Takanori Teshima

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)551-556
Number of pages6
JournalJournal of Immunology
Volume174
Issue number1
Publication statusPublished - Jan 1 2005

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Natural Killer T-Cells
Glycolipids
Graft vs Host Disease
T-Lymphocytes
Interleukin-4
Galactosylceramides
Cytokines
Ligands
Artificial Cells
Injections
Homologous Transplantation
Bone Marrow Transplantation
Morbidity
Mortality
Serum
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Hashimoto, D., Asakura, S., Miyake, S., Yamamura, T., Van Kaer, L., Liu, C., ... Teshima, T. (2005). Stimulation of host NKT cells by synthetic glycolipid regulates acute graft-versus-host disease by inducing Th2 polarization of donor T cells. Journal of Immunology, 174(1), 551-556.

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 journalArticle

Hashimoto, D, Asakura, S, Miyake, S, Yamamura, T, Van Kaer, L, Liu, C, Tanimoto, M & Teshima, T 2005, 'Stimulation of host NKT cells by synthetic glycolipid regulates acute graft-versus-host disease by inducing Th2 polarization of donor T cells', Journal of Immunology, vol. 174, no. 1, pp. 551-556.
Hashimoto, Daigo ; Asakura, Shoji ; Miyake, Sachiko ; Yamamura, Takashi ; Van Kaer, Luc ; Liu, Chen ; Tanimoto, Mitsune ; Teshima, Takanori. / Stimulation of host NKT cells by synthetic glycolipid regulates acute graft-versus-host disease by inducing Th2 polarization of donor T cells. In: Journal of Immunology. 2005 ; Vol. 174, No. 1. pp. 551-556.
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