CD3-specific antibodies restore self-tolerance: mechanisms and clinical applications

Curr Opin Immunol. 2005 Dec;17(6):632-7. doi: 10.1016/j.coi.2005.09.011. Epub 2005 Oct 7.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • CD3 Complex / immunology*
  • Humans
  • Mice
  • Self Tolerance*

Substances

  • Antibodies, Monoclonal
  • CD3 Complex