Human CD14hi monocytes and myeloid dendritic cells provide a cell contact-dependent costimulatory signal for early CD40 ligand expression

Blood. 2011 Feb 3;117(5):1585-94. doi: 10.1182/blood-2008-01-130252. Epub 2010 Jul 15.


CD40L on CD4(+) T cells plays a vital role in the activation of antigen-presenting cells, thus catalyzing a positive feedback loop for T-cell activation. Despite the pivotal juxtaposition of CD40L between antigen-presenting cells and T-cell activation, only a T-cell receptor stimulus is thought to be required for early CD40L surface expression. We show, for the first time, that CD40L expression on peripheral blood CD4(+) T cells is highly dependent on a cell-cell interaction with CD14(hi)CD16(-) monocytes. Interactions with ICAM-1, LFA-3, and to a lesser extent CD80/CD86 contribute to this enhancement of CD40L expression but are not themselves sufficient. The contact-mediated increase in CD40L expression is dependent on new mRNA and protein synthesis. Circulating myeloid dendritic cells also possess this costimulatory activity. By contrast, CD14(lo)CD16(+) monocytes, plasmacytoid dendritic cells, B-cell lymphoma lines, and resting, activated, and Epstein-Barr virus-immortalized primary B cells all lack the capacity to up-regulate early CD40L. The latter indicates that a human B cell cannot activate its cognate T cell to deliver CD40L-mediated help. This finding has functional implications for the role of biphasic CD40L expression, suggesting that the early phase is associated with antigen-presenting cell activation, whereas the late phase is related to B-cell activation.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Antigen-Presenting Cells
  • Blotting, Northern
  • Blotting, Western
  • CD4-Positive T-Lymphocytes
  • CD40 Antigens / metabolism*
  • CD40 Ligand / genetics
  • CD40 Ligand / metabolism*
  • CD58 Antigens / genetics
  • CD58 Antigens / metabolism
  • Cell Adhesion*
  • Cell Communication
  • Cells, Cultured
  • Dendritic Cells / metabolism*
  • Flow Cytometry
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lipopolysaccharide Receptors / metabolism*
  • Lymphocyte Activation
  • Monocytes / cytology
  • Monocytes / metabolism*
  • Myeloid Cells / metabolism*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction


  • CD40 Antigens
  • CD58 Antigens
  • Lipopolysaccharide Receptors
  • RNA, Messenger
  • Intercellular Adhesion Molecule-1
  • CD40 Ligand