CD3-specific antibody-induced active tolerance: from bench to bedside.
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.
Chatenoud
Lucienne
L
Centre de l'Association Claude Bernard sur les Maladies Autoimmunes and Hôpital Necker Enfants Malades IRNEM, 161 Rue de Sèvres, 75015 Paris, France. chatenoud@necker.fr
D000818:Animals; D017252:CD3 Complex / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D018448:Models, Immunological; D016853:Muromonab-CD3 / Q000235:genetics / Q000627:therapeutic use*; D015202:Protein Engineering; D016176:T-Lymphocyte Subsets / Q000276:immunology
D017252:CD3 Complex; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3