Does lymphopenia preclude restoration of immune homeostasis? The particular case of type 1 diabetes

Autoimmunity Reviews
Enosh M AskenasyJean-Jaques Askenasy

Abstract

Induction of hematopoietic chimerism initiates tolerizing processes that often restore control over autoimmune reactions: graft versus autoimmunity reaction. In view of the limited capacity of autologous bone marrow transplants and some cases of persistent autoimmune diabetes after allogeneic transplants, we hypothesize that the preparative conditioning regimens adopted from the oncological setting are suboptimal approaches to rebooting the immune system. In general, homeostatic expansion under lymphopenic conditions favors the recovery and development of cytotoxic T cells. Autoimmune diabetes is a particular case in which debulking is ineffective due to resistance of the effector cells to depletion by conventional immunosuppressive therapies. Furthermore, resetting of immune activity is impaired by lymphopenia-induced proliferation of residual diabetogenic clones and delayed recovery of suppressor cells. For control of the autoimmune reaction it is essential to design immunomodulatory approaches that overcome rejection while avoiding homeostatic expansion of residual diabetogenic clones.

References

May 1, 1989·European Journal of Immunology·M DardenneJ F Bach
Feb 1, 1996·Immunological Reviews·P A GleesonI R van Driel
Aug 22, 2000·The Journal of Experimental Medicine·A W GoldrathM J Bevan
Sep 18, 2002·The Journal of Experimental Medicine·Adam G Schrum, Laurence A Turka
Sep 28, 2002·Diabetes·Sheela RamanathanPhilippe Poussier
Feb 20, 2003·The Journal of Experimental Medicine·Thomas BarthlottBrigitta Stockinger
May 20, 2003·Journal of Autoimmunity·Brigitte DecallonneChantal Mathieu
Dec 3, 2003·Nature Medicine·Zihao WuLaurence A Turka
Feb 28, 2004·Journal of Autoimmunity·Raymond J SteptoeGrant Morahan
Jun 9, 2004·The Journal of Experimental Medicine·Qizhi TangJeffrey A Bluestone
Feb 7, 2006·Trends in Immunology·Zoltán FehérvariShimon Sakaguchi
Mar 17, 2007·Journal of Autoimmunity·Abul K AbbasBirgit Knoechel
Jul 20, 2007·Immunology and Cell Biology·Ayelet KaminitzNadir Askenasy
Jan 29, 2008·Journal of Autoimmunity·Alberto M Marmont
Feb 5, 2008·Journal of Autoimmunity·Richard K BurtWalter Barr
Mar 25, 2008·Experimental Hematology·Michael J HallerDesmond A Schatz
Jun 20, 2008·Proceedings of the National Academy of Sciences of the United States of America·Christine BourgeoisBrigitta Stockinger
Nov 22, 2008·Blood·Anna ShvetsGérald J Prud'homme
Apr 28, 2009·Autoimmunity Reviews·Núria AlonsoEva Martínez-Cáceres
Oct 6, 2009·Journal of Autoimmunity·Isaac YanivJerry Stein
Dec 9, 2009·Autoimmunity Reviews·Andrea T BorchersM E Gershwin
Dec 18, 2009·Nature Immunology·Harald von Boehmer, Fritz Melchers

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Citations

May 12, 2011·British Journal of Pharmacology·E Y ZhangT M Yankee
Jan 10, 2012·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Shai YarkoniNadir Askenasy

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