Less is more: the detrimental consequences of immunosuppressive therapy in the treatment of type-1 diabetes

International Reviews of Immunology
Nadir Askenasy

Abstract

The prevalent current approach to type 1 diabetes (T1D) is the abrogation of pathogenic potential by immunosuppressive therapy, an intuitive approach aiming to slow down disease progression by the reduction of pathogenic burden. In spite of promising initial results in rodent models, there has been little efficacy of most lymphoreductive strategies in human subjects. Our analysis suggests that lymphopenia is the common denominator of ineffective immunosuppressive therapies: Immune rebound from lymphopenia is associated per se with increased susceptibility to immune reactivity, including relapse of autoimmunity. In addition, immune homeostasis and self-tolerance are not restored. These considerations raise the following question: What is the allowed degree of immunosuppressive therapy that does not elicit recurrent autoimmunity. More effective therapeutic strategies include targeted deletion of pathogenic cells, preferably in the pancreatic islets and regional lymphatics using selective T cell activation markers, re-education and remodeling of effector responses.

References

Apr 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·T MakiJ Porter
Sep 8, 1988·The New England Journal of Medicine·J SilversteinS Johnson
Jan 1, 1986·Transplantation·H J HahnR Warzock
Jan 15, 1983·British Medical Journal·J LudvigssonA Lernmark
May 1, 1995·The Journal of Experimental Medicine·E LargerC Boitard
Jul 1, 1994·Clinical and Experimental Immunology·P SaïE Gouin
Jan 4, 1994·Proceedings of the National Academy of Sciences of the United States of America·L ChatenoudJ F Bach
Mar 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S KimM S Lee
Jul 20, 2000·Clinical Immunology : the Official Journal of the Clinical Immunology Society·B A Buckingham, C I Sandborg
Aug 22, 2000·The Journal of Experimental Medicine·C D Surh, J Sprent
Nov 28, 2000·European Journal of Immunology·N L La GrutaP A Gleeson
May 4, 2001·Journal of Autoimmunity·I R Cohen
May 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Corinne TanchotBruno Lucas
May 31, 2002·The New England Journal of Medicine·Kevan C HeroldJeffrey A Bluestone
Jan 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amy E Troy, Hao Shen
Feb 28, 2004·Journal of Autoimmunity·Raymond J SteptoeGrant Morahan
Mar 26, 2005·Immunology Letters·Alexander Khoruts, Joanne M Fraser
Apr 15, 2005·Journal of Autoimmunity·Karine HadayaFlora Zavala
Jun 24, 2005·The New England Journal of Medicine·Bart KeymeulenLucienne Chatenoud
Jul 15, 2005·Annals of the New York Academy of Sciences·Hester A Doyle, Mark J Mamula
Nov 1, 2005·Journal of Autoimmunity·Linda S WickerLaurence B Peterson
Dec 2, 2005·International Reviews of Immunology·Kevin S Goudy, Roland Tisch
Jan 26, 2006·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Michal Pearl-YafeNadir Askenasy
Apr 22, 2006·The Journal of Clinical Investigation·Damien BressonMatthias von Herrath
Aug 4, 2006·The Journal of Clinical Investigation·Brian T FifeJeffrey A Bluestone

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