The role of CD40 in peripheral T cell tolerance and immunity (original) (raw)

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.

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Authors and Affiliations

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

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  1. L. Diehl
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  2. A.T. Den Boer
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  3. E.I.H. van der Voort
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  4. C.J.M. Melief
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  5. R. Offringa
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  6. R.E.M. Toes
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Diehl, L., Den Boer, A., van der Voort, E. et al. The role of CD40 in peripheral T cell tolerance and immunity.J Mol Med 78, 363–371 (2000). https://doi.org/10.1007/s001090000126

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