Prevention of type 1 diabetes by invariant NKT cells is independent of peripheral CD1d expression

Jan Novak, Lucie Beaudoin, Se Ho Park, Thibault Griseri, Luc Teyton, Albert Bendelac, Agnès Lehuen

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Invariant NKT (iNKT) cells can prevent diabetes by inhibiting the differentiation of anti-islet T cells. We recently showed that neither iNKT cell protection against diabetes nor iNKT cell inhibition of T cell differentiation in vitro requires cytokines such as IL-4, IL-10, IL-13, and TGF-β. In contrast, cell-cell contacts were required for iNKT cell inhibition of T cell differentiation in vitro. The present study was designed to determine whether the CD1d molecule is involved in the inhibitory function of iNKT cells. Experiments were performed in vitro and in vivo, using cells lacking CD1d expression. The in vivo experiments used CD1d-deficient mice that were either reconstituted with iNKT cells or expressed a CD1d transgene exclusively in the thymus. Both mouse models had functional iNKT cells in the periphery, even though CD1d was not expressed in peripheral tissues. Surprisingly, both in vitro inhibition of T cell differentiation by iNKT cells and mouse protection against diabetes by iNKT cells were CD1d-independent. These results reveal that iNKT cells can exert critical immunoregulatory effects in the absence of CD1d recognition and that different molecular interactions are involved in iNKT cell functions.

Original languageEnglish
Pages (from-to)1332-1340
Number of pages9
JournalJournal of Immunology
Volume178
Issue number3
DOIs
Publication statusPublished - 2007 Feb 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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