The CD40/CD154 receptor/ligand dyad

Cell Mol Life Sci. 2001 Jan;58(1):4-43. doi: 10.1007/pl00000776.


Until recently, the expression and primary function of the cell surface receptor CD40 and its ligand CD154 were considered restricted to B and T lymphocytes, and their interactions required for the thymus-dependent humoral response. However, current work from several groups challenges this view of the CD40/CD154 dyad as a mere mediator of lymphocyte communication. A variety of non-lymphocytic cell types express both receptor and ligand, including hematopoetic and non-hematopoetic cells, such as monocytes, basophils, eosinophils, dendritic cells, fibroblasts, smooth muscle, and endothelial cells. Accordingly, ligation of CD40 mediates a broad variety of immune and inflammatory responses, such as the expression of adhesion molecules, cytokines, matrix-degrading enzymes, prothrombotic activities, and apoptotic mediators. Consequently, CD40 signaling has been associated with pathogenic processes of chronic inflammatory diseases, such as autoimmune diseases, neurodegenerative disorders, graft-versus-host disease, cancer, and atherosclerosis. This review focuses on the synthesis and structure of CD40 and outlines CD154/CD40 signaling pathways, and emphasizes the previously unexpected importance of the CD40/CD154 receptor/ligand dyad in a spectrum of immunoregulatory processes and prevalent human diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • CD40 Antigens / chemistry
  • CD40 Antigens / genetics
  • CD40 Antigens / immunology*
  • CD40 Antigens / metabolism*
  • CD40 Ligand / genetics
  • CD40 Ligand / immunology*
  • CD40 Ligand / metabolism*
  • Cells / metabolism
  • Gene Expression Regulation
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Lymphocyte Activation
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Signal Transduction*


  • CD40 Antigens
  • CD40 Ligand