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

78 Citations (Scopus)

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
DOIs
Publication statusPublished - Jan 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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