CD3-specific antibodies restore self-tolerance: mechanisms and clinical applications.
The treatment of autoimmune diseases using conventional chemical immunosuppressants has short-term effects, imposing the need for chronic treatment with its risks of over-immunosuppression. CD3-specific monoclonal antibodies can restore self-tolerance in a durable fashion after a single short-term treatment, as demonstrated in several experimental models and clinically in recent-onset insulin-dependent diabetes. Disease remission involves first an immediate 'freezing' of the autoimmune response, which is linked to CD3-specific antibody-induced antigenic modulation of CD3-TCR complex at the T lymphocyte surface, followed by 'resetting' of TGF-beta-dependent T-cell mediated immunoregulation. Tolerance induction is demonstrated by persisting disease protection in spite of recovery of full immunocompetence to unrelated antigens.
Chatenoud
Lucienne
L
Université René Descartes Paris 5, INSERM U580, Hôpital Necker Enfants Malades, 161 Rue de Sèvres, 75015 Paris, France. chatenoud@necker.fr
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D006801:Humans; D051379:Mice; D017634:Self Tolerance
D000911:Antibodies, Monoclonal; D017252:CD3 Complex