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

Current Opinion in Immunology
Lucienne Chatenoud

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.

References

Apr 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·T MakiJ Porter
Nov 1, 1982·European Journal of Immunology·L ChatenoudJ F Bach
Jun 1, 1994·The Journal of Clinical Investigation·K J ParlevlietP T Schellekens
Jan 4, 1994·Proceedings of the National Academy of Sciences of the United States of America·L ChatenoudJ F Bach
Apr 21, 1997·The Journal of Experimental Medicine·J A SmithJeffrey A Bluestone
Feb 12, 1998·The Journal of Experimental Medicine·J TianD L Kaufman
Jun 24, 1998·Transplantation Proceedings·E S WoodleJ R Thistlethwaite
Nov 28, 2001·Immunological Reviews·L ChatenoudJeffrey A Bluestone
May 31, 2002·The New England Journal of Medicine·Diabetes Prevention Trial--Type 1 Diabetes Study Group
May 31, 2002·The New England Journal of Medicine·Kevan C HeroldJeffrey A Bluestone
Aug 17, 2002·Current Opinion in Immunology·Thomas WekerleM Sykes
Aug 17, 2002·Current Opinion in Immunology·Scott H Adler, Laurence A Turka
Feb 4, 2003·Nature Reviews. Immunology·Lucienne Chatenoud
Feb 14, 2004·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Bernhard J HeringJeffrey A Bluestone
Mar 23, 2004·Annual Review of Immunology·Sergio A QuezadaRandolph J Noelle
Jan 1, 1984·Immunology Today·L Chatenoud, J F Bach

Citations

Jun 11, 2008·Immunologic Research·Bo Wang, Roland Tisch
Dec 5, 2008·Immunologic Research·Bo Wang, Roland Tisch
Nov 23, 2006·The Journal of Experimental Medicine·Brian T FifeJeffrey A Bluestone
Mar 7, 2014·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Anne JörnsSigurd Lenzen
Sep 26, 2007·The Journal of Experimental Medicine·Michael R Ehrenstein, Claudia Mauri
Feb 4, 2011·Seminars in Immunology·Brigitta StockingerMarc Veldhoen
Aug 25, 2010·Best Practice & Research. Clinical Rheumatology·Faye A H Cooles, John D Isaacs
Sep 23, 2008·Journal of the Neurological Sciences·Hirofumi OchiHoward L Weiner
Dec 14, 2007·Journal of Neuroimmunology·Richard A O'Connor, Stephen M Anderton
Jan 15, 2008·Journal of Autoimmunity·Michal AbrahamHoward L Weiner
Nov 6, 2007·Trends in Molecular Medicine·Ramireddy Bommireddy, Thomas Doetschman
Oct 11, 2012·Immunological Reviews·Michael S Kuhns, Hemant B Badgandi
Oct 3, 2006·Current Opinion in Immunology·Lucienne Chatenoud
Feb 14, 2006·Immunity·Michael S KuhnsK Christopher Garcia
Mar 5, 2008·Diabetes·Brett PhillipsNick Giannoukakis
May 11, 2016·Immunotherapy·Chantal Kuhn, Howard L Weiner
Feb 16, 2017·Mucosal Immunology·A Pascual-ReguantE Esplugues
Mar 1, 2006·Expert Review of Clinical Immunology·A Zwiers, G Bouma
Apr 8, 2006·Physiological Reviews·Alain Tedgui, Ziad Mallat
Sep 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christine Bourgeois, Brigitta Stockinger
Oct 17, 2017·Frontiers in Immunology·Marta Consuegra-FernándezFrancisco Lozano

Related Concepts

Monoclonal Antibodies
Autoimmune Diseases
CD3 Antigens
Self Tolerance

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Antigenic Modulation

Antigenic modulation occurs when an antibody cross-links antigens on a cell surface, causing the antigens to become internalized. This can lead to therapeutic failure of monoclonal antibodies as the expression of the antigen becomes decreased on target cells. Find the latest research on antigenic modulation here.