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

Abstract

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.

• Authors: Lucienne Chatenoud
• Journal: Nature reviews. Immunology (Nat Rev Immunol) Vol. 3 Issue 2 Pg. 123-32 (Feb 2003) ISSN: 1474-1733 [Print] England
• PMID: 12563296 (Publication Type: Journal Article, Review)

Chemical References

• CD3 Complex
• Immunosuppressive Agents
• Muromonab-CD3

Topics

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