CD3-specific antibody-induced active tolerance: from bench to bedside

Nat Rev Immunol. 2003 Feb;3(2):123-32. doi: 10.1038/nri1000.


Although they were used initially as non-specific immunosuppressants in transplantation, CD3-specific monoclonal antibodies have elicited renewed interest owing to their capacity to induce immune tolerance. In mouse models of autoimmune diabetes, CD3-specific antibodies induce stable disease remission by restoring tolerance to pancreatic beta-cells. This phenomenon was extended recently to the clinic--preservation of beta-cell function in recently diagnosed patients with diabetes was achieved by short-term administration of a CD3-specific antibody. CD3-specific antibodies arrest ongoing disease by rapidly clearing pathogenic T cells from the target. Subsequently, they promote long-term T-cell-mediated active tolerance. Recent data indicate that transforming growth factor-beta-dependent CD4+CD25+ regulatory T cells might have a central role in this effect.

Publication types

  • Review

MeSH terms

  • Animals
  • CD3 Complex / immunology*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / therapy
  • Humans
  • Immune Tolerance*
  • Immunosuppressive Agents / therapeutic use*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred NOD
  • Models, Immunological
  • Muromonab-CD3 / genetics
  • Muromonab-CD3 / therapeutic use*
  • Protein Engineering
  • T-Lymphocyte Subsets / immunology


  • CD3 Complex
  • Immunosuppressive Agents
  • Muromonab-CD3