Send to

Choose Destination
See comment in PubMed Commons below
J Clin Invest. 2004 Jun;113(11):1631-40.

The clinical implication and molecular mechanism of preferential IL-4 production by modified glycolipid-stimulated NKT cells.

Author information

Department of Immunology, National Institute of Neuroscience, National Center for Neuroscience and Psychiatry, Tokyo, Japan.


OCH, a sphingosine-truncated analog of alpha-galactosylceramide (alphaGC), is a potential therapeutic reagent for a variety of Th1-mediated autoimmune diseases through its selective induction of Th2 cytokines from natural killer T (NKT) cells. We demonstrate here that the NKT cell production of IFN-gamma is more susceptible to the sphingosine length of glycolipid ligand than that of IL-4 and that the length of the sphingosine chain determines the duration of NKT cell stimulation by CD1d-associated glycolipids. Furthermore, IFN-gamma production by NKT cells requires longer T cell receptor stimulation than is required for IL-4 production by NKT cells stimulated either with immobilized mAb to CD3 or with immobilized "alphaGC-loaded" CD1d molecules. Interestingly, transcription of IFN-gamma but not that of IL-4 was sensitive to cycloheximide treatment, indicating the intrinsic involvement of de novo protein synthesis for IFN-gamma production by NKT cells. Finally, we determined c-Rel was preferentially transcribed in alphaGC-stimulated but not in OCH-stimulated NKT cells and was essential for IFN-gamma production by activated NKT cells. Given the dominant immune regulation by the remarkable cytokine production of ligand-stimulated NKT cells in vivo, in comparison with that of (antigen-specific) T cells or NK cells, the current study confirms OCH as a likely therapeutic reagent for use against Th1-mediated autoimmune diseases and provides a novel clue for the design of drugs targeting NKT cells.

[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Society for Clinical Investigation Icon for PubMed Central
    Loading ...
    Support Center