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

Nature Reviews. Immunology
Lucienne Chatenoud

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.

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Related Concepts

Diabetes, Autoimmune
Natural Immunosuppression
Immunosuppressive Agents
Lymphocyte Activation
Protein Engineering
T-Lymphocyte Subsets
Mice, Inbred NOD
Orthoclone OKT3
CD3 Antigens

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