Immunotherapy targeting the CD40/CD154 costimulatory pathway for treatment of autoimmune disease

Lawrence M. Howard, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations


The CD154-CD40 ligand pair interaction plays a central role in both induction of the immune response and in immune effector functions. Indeed, many animal disease models and human autoimmune diseases have demonstrated a central role for CD154 expression. The expression of CD154 is very tightly regulated by the immune system through a number of non-redundant overlapping mechanisms that ensure its limited initial induction, along with its temporal maintenance and rapid elimination from the cell surface, and its functional neutralization by the release of soluble CD40. In this review, we discuss the current state of understanding of CD154 regulation during the activation of the immune system and describe numerous strategic mechanisms by which modulation of CD154-CD40 interactions may be applied to treat autoimmune disease.

Original languageEnglish (US)
Pages (from-to)411-418
Number of pages8
Issue number5
StatePublished - Aug 2004


  • Autoimmunity
  • CD154
  • CD40
  • Cancer
  • Dendritic cell
  • Regulation
  • T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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