The role of CD40 in peripheral T cell tolerance and immunity

J Mol Med (Berl). 2000;78(7):363-71. doi: 10.1007/s001090000126.


CD40 and CD40 ligand (CD40L) have been implicated as important molecules for the transformation of nonactivated antigen-presenting cells (APC) into cells that are potent inducers of cytotoxic T lymphocyte (CTL) immunity. The onset of a successful immune response lies within the control of the CD4+ T helper cells which, after specific antigen recognition, can up-regulate CD40L and subsequently activate APC through CD40 signaling. Triggering of CD40 with antibodies in vivo can replace the need for CD40L-expressing CD4+ T helper cells for cross-priming of CTL. Blocking of CD40-CD40L interactions can also have profound effects on the generation of T cell immunity. Interestingly, differential involvement of CD40/CD40L in immune responses can be observed between various immunological sites in the body. In most sites of the periphery interruption of CD40-CD40L interactions can lead to the induction of T cell tolerance whereas in mucosal tissues this interruption can lead to abrogation of T cell tolerance. Furthermore, in vivo CD40 activation can convert specific T cell tolerance following peptide vaccination into efficient T cell priming. Thus intervention of CD40-CD40L interactions can result in enhancement or down-modulation of T cell reactivity and therefore modulation of these interactions may form the foundation of new treatment modalities directed against malignancies, allergies, organ rejections and autoimmunity.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD40 Antigens / physiology*
  • CD40 Ligand / physiology
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Immune System / physiology
  • Lymphocyte Activation
  • Models, Biological
  • Peptides / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Helper-Inducer / immunology
  • Up-Regulation
  • Vaccines / immunology


  • CD40 Antigens
  • Histocompatibility Antigens Class I
  • Peptides
  • Vaccines
  • CD40 Ligand