CD40 ligation releases immature dendritic cells from the control of regulatory CD4+CD25+ T cells

Immunity. 2003 Dec;19(6):877-89. doi: 10.1016/s1074-7613(03)00327-3.


We report that disruption of CD154 in nonobese diabetic (NOD) mice abrogates the helper function of CD4+CD25- T cells without impairing the regulatory activity of CD4+CD25+ T cells. Whereas CD4+ T cells from NOD mice enhanced a diabetogenic CD8+ T cell response in monoclonal TCR-transgenic NOD mice, CD4+ T cells from NOD.CD154(-/-) mice actively suppressed it. Suppression was mediated by regulatory CD4+CD25+ T cells capable of inhibiting CD8+ T cell responses induced by peptide-pulsed dendritic cells (DCs), but not peptide/MHC monomers. It involved inhibition of DC maturation, did not occur in the presence of CD154+ T-helper cells, and could be inhibited by activation of DCs with LPS, CpG DNA, or an agonistic anti-CD40 mAb. Thus, in at least some genetic backgrounds, CD154-CD40 interactions and innate stimuli release immature DCs from suppression by CD4+CD25+ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD40 Antigens / metabolism*
  • CD40 Ligand / genetics
  • CD40 Ligand / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • CpG Islands / physiology
  • Dendritic Cells / metabolism*
  • Diabetes Mellitus / etiology
  • Diabetes Mellitus / metabolism
  • Macrophages
  • Mice
  • Receptors, Interleukin-2 / metabolism*


  • CD40 Antigens
  • Receptors, Interleukin-2
  • CD40 Ligand