Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient

Cell Death and Differentiation
E SunY Shi

Abstract

Cell death through apoptosis plays a critical role in regulating cellular homeostasis. Whether the disposal of apoptotic cells through phagocytosis can actively induce immune tolerance in vivo, however, remains controversial. Here, we report in a rat model that without using immunosuppressants, transfusion of apoptotic splenocytes from the donor strain prior to transplant dramatically prolonged survival of heart allografts. Histological analysis verified that rejection signs were significantly ameliorated. Splenocytes from rats transfused with donor apoptotic cells showed a dramatically decreased response to donor lymphocyte stimulation. Most importantly, blockade of phagocytosis in vivo, either with gadolinium chloride to disrupt phagocyte function or with annexin V to block binding of exposed phosphotidylserine to its receptor on phagocytes, abolished the beneficial effect of transfused apoptotic cells on heart allograft survival. Our results demonstrate that donor apoptotic cells promote specific allograft acceptance and that phagocytosis of apoptotic cells in vivo plays a crucial role in maintaining immune tolerance.

References

Oct 12, 1978·The New England Journal of Medicine·G Opelz, P I Terasaki
Sep 1, 1988·Investigative Radiology·P B DeanM Kormano
Jan 1, 1994·Annual Review of Immunology·P Matzinger
Mar 1, 1993·Immunology Today·J SavillC Haslett
Jul 1, 1996·The Journal of Surgical Research·K SatoT Maekawa
Oct 1, 1996·Journal of Leukocyte Biology·C R RolandM W Flye
May 1, 1997·Toxicologic Pathology·A J SpencerE Harpur
Dec 6, 1997·Nature·R E VollI Girkontaite
Dec 5, 1998·Transfusion·F FrabettiR Conte
Mar 3, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C R RolandM W Flye
Nov 5, 1999·Nature Medicine·S GallucciP Matzinger
Nov 5, 1999·Current Opinion in Hematology·C T Smit Sibinga
Jan 1, 2000·Diabetes·J D TrudeauD T Finegood
Feb 24, 2000·Transfusion·F FrabettiR Conte
Mar 29, 2000·Scandinavian Journal of Immunology·E SunW Gao
Apr 18, 2000·Rheumatic Diseases Clinics of North America·F AndradeA Rosen
Aug 10, 2000·American Journal of Surgery·J M RabkinA J Olyaei
Oct 26, 2000·Nature·J Savill, V Fadok
Mar 21, 2001·Apoptosis : an International Journal on Programmed Cell Death·H M LorenzJ R Kalden
Oct 10, 2001·Current Biology : CB·P M HensonV A Fadok
Mar 28, 2002·Pharmacology & Therapeutics·E W Sun, Y F Shi
Dec 4, 2003·Science·Ming O LiRichard A Flavell

❮ Previous
Next ❯

Citations

Feb 9, 2010·Apoptosis : an International Journal on Programmed Cell Death·Adrian E Morelli, Adriana T Larregina
Apr 15, 2009·Nature Reviews. Immunology·Douglas R GreenGuido Kroemer
Aug 19, 2007·Transplantation·Philippe SaasSylvain Perruche
Jun 30, 2010·The Journal of Cell Biology·Michael R Elliott, Kodi S Ravichandran
Mar 5, 2013·La Presse médicale·Sylvain Perruche, Philippe Saas
Jun 9, 2012·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·P SaasS Perruche
Apr 13, 2011·Journal of the Neurological Sciences·Elena TitovaAndre Obenaus
Mar 15, 2011·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·M MatignonP Grimbert
Jun 6, 2008·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·P SaasS Perruche
Aug 8, 2007·Medical Hypotheses·Erwei Sun
Apr 29, 2009·European Journal of Clinical Investigation·H J AnkersmitB K Podesser
Jun 21, 2006·Scandinavian Journal of Immunology·G LiuY Zhao
Sep 11, 2008·Scandinavian Journal of Immunology·Y WangZ K Chen
Oct 21, 2010·Annals of the New York Academy of Sciences·Philippe SaasSylvain Perruche
Oct 21, 2010·Annals of the New York Academy of Sciences·Masato TanakaChun-Hong Qiu
Feb 1, 2011·Transplant International : Official Journal of the European Society for Organ Transplantation·Maria-Luisa del RioJose-Ignacio Rodriguez-Barbosa
Dec 9, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Minggang ZhangXuetao Cao
Jun 27, 2007·The American Journal of Pathology·Lars-Peter Erwig, Peter M Henson
Oct 24, 2006·The Journal of Surgical Research·Hongchi JiangXueying Sun
Dec 17, 2014·Acta histochemica·María Clara CarouDaniel Marcelo Lombardo
Oct 4, 2014·Frontiers in Immunology·Marta Monguió-TortajadaFrancesc E Borràs
Aug 12, 2014·Cellular & Molecular Immunology·Haibin Li, Bingyi Shi
Oct 28, 2016·Apoptosis : an International Journal on Programmed Cell Death·Lucian BeerHendrik Jan Ankersmit
Mar 14, 2017·Nature Reviews. Immunology·Nader YatimMatthew L Albert
Oct 4, 2012·Cell Transplantation·M M SklavosJ D Piganelli
Oct 31, 2014·Inflammatory Bowel Diseases·Md Mesbah Uddin AnsaryYoshikazu Kinoshita
Nov 28, 2017·Current Transplantation Reports·Anil Dangi, Xunrong Luo
Feb 1, 2014·Nature Reviews. Immunology·Ivan K H PoonKodi S Ravichandran
Sep 1, 2019·Transplant International : Official Journal of the European Society for Organ Transplantation·Jordi OchandoAngus W Thomson
Jun 14, 2014·Current Opinion in Organ Transplantation·Adrian E Morelli, Angus W Thomson
Jun 14, 2018·Nature Reviews. Nephrology·Yufang ShiYing Wang
Aug 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Guangwen RenYufang Shi
Mar 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chun-Hong QiuMasato Tanaka

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis