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-β-dependent T-cell mediated immunoregulation. Tolerance induction is demonstrated by persisting disease protection in spite of recovery of full immunocompetence to unrelated antigens.