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 -cells. This phenomenon was extended recently to the clinic — preservation of -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--dependent CD4⁺CD25⁺ regulatory T cells might have a central role in this effect.

Author affiliations

1. Centre de l'Association Claude Bernard sur les Maladies Autoimmunes and Hôpital Necker Enfants Malades IRNEM, 161 Rue de Sèvres, 75015 Paris, France.
   Email: chatenoud@necker.fr