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Journal of Molecular Medicine

, Volume 78, Issue 7, pp 363–371 | Cite as

The role of CD40 in peripheral T cell tolerance and immunity

  • L. Diehl
  • A.T. Den Boer
  • E.I.H. van der Voort
  • C.J.M. Melief
  • R. Offringa
  • R.E.M. Toes
Review

Abstract

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.

CD40/CD40L T cell tolerance T cell immunity Dendritic cell Cytotoxic T Lymphocyte T helper cell 

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Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • L. Diehl
    • 1
  • A.T. Den Boer
    • 1
  • E.I.H. van der Voort
    • 1
  • C.J.M. Melief
    • 1
  • R. Offringa
    • 1
  • R.E.M. Toes
    • 1
  1. 1.Department of Immunohematology and Blood Transfusion, Medical Center, Leiden University, Albinusdreef 2, 2333 ZA, LeidenThe Netherlands

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