Format

Send to

Choose Destination
See comment in PubMed Commons below
J Immunol. 2008 Aug 15;181(4):2438-45.

Ligand-dependent induction of noninflammatory dendritic cells by anergic invariant NKT cells minimizes autoimmune inflammation.

Author information

1
Julia McFarlane Diabetes Research Centre, Department of Biochemistry and Molecular Biology, The University of Calgary, Canada.

Erratum in

  • J Immunol. 2008 Oct 15;181(8):5803. Xu, Bo-You [corrected to Xu, Bao-You].

Abstract

Stimulated by an agonistic ligand, alpha-galactosylceramide (alphaGalCer), invariant NKT (iNKT) cells are capable of both eliciting antitumor responses and suppressing autoimmunity, while they become anergic after an initial phase of activation. It is unknown how iNKT cells act as either activators or regulators in different settings of cellular immunity. We examined effects of alphaGalCer administration on autoimmune inflammation and characterized phenotypes and functional status of iNKT cells and dendritic cells in alphaGalCer-treated NOD mice. Although iNKT cells became and remained anergic after the initial exposure to their ligand, anergic iNKT cells induce noninflammatory DCs in response to alphaGalCer restimulation, whereas activated iNKT cells induce immunogenic maturation of DCs in a small time window after the priming. Induction of noninflammatory DCs results in the activation and expansion of islet-specific T cells with diminished proinflammatory cytokine production. The noninflammatory DCs function at inflammation sites in an Ag-specific fashion, and the persistence of noninflammatory DCs critically inhibits autoimmune pathogenesis in NOD mice. Anergic differentiation is a regulatory event that enables iNKT cells to transform from promoters to suppressors, down-regulating the ongoing inflammatory responses, similar to other regulatory T cells, through a ligand-dependent mechanism.

PMID:
18684934
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center