B-cells promote intra-islet CD8+ cytotoxic T-cell survival to enhance type 1 diabetes

Diabetes
Gillian M BrodieE Allison Green

Abstract

To determine the role of B-cells in promoting CD8(+) T-cell-mediated beta cell destruction in chronically inflamed islets. RESEARCH DESIGN AND METHODS-RIP: TNFalpha-NOD mice were crossed to B-cell-deficient NOD mice, and diabetes development was monitored. We used in vitro antigen presentation assays and in vivo administration of bromodeoxyuridine coupled to flow cytometry assays to assess intra-islet T-cell activation in the absence or presence of B-cells. CD4(+)Foxp3(+) activity in the absence or presence of B-cells was tested using in vivo depletion techniques. Cytokine production and apoptosis assays determined the capacity of CD8(+) T-cells transform to cytotoxic T-lymphocytes (CTLs) and survive within inflamed islets in the absence or presence of B-cells. B-cell deficiency significantly delayed diabetes development in chronically inflamed islets. Reintroduction of B-cells incapable of secreting immunoglobulin restored diabetes development. Both CD4(+) and CD8(+) T-cell activation was unimpaired by B-cell deficiency, and delayed disease was not due to CD4(+)Foxp3(+) T-cell suppression of T-cell responses. Instead, at the CTL transition stage, B-cell deficiency resulted in apoptosis of intra-islet CTLs. In inflamed islets, ...Continue Reading

References

Mar 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·W HeldC Mueller
May 1, 1996·The Journal of Experimental Medicine·M S Asano, R Ahmed
Jun 1, 1997·Research in Immunology·F S Wong, C A Janeway
Dec 31, 1997·The Journal of Experimental Medicine·J VerdaguerP Santamaria
Aug 18, 1999·Immunological Reviews·E A Green, R A Flavell
Jan 13, 2000·Current Opinion in Immunology·E A Green, R A Flavell
Mar 22, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·R T GraserD V Serreze
Oct 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·H NoorchashmA Naji
Oct 6, 2001·The New England Journal of Medicine·S MartinB O Roep
Oct 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S A GreeleyA Naji
Jan 11, 2003·Science·Shohei HoriShimon Sakaguchi
Jun 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Scott M LiebermanTeresa P DiLorenzo
Apr 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pablo A SilveiraDavid V Serreze
Sep 28, 2004·Diabetes·F Susan WongMark J Shlomchik
Mar 26, 2005·Immunological Reviews·Teresa P DiLorenzo, David V Serreze
Apr 4, 2006·Trends in Endocrinology and Metabolism : TEM·Pablo A Silveira, Shane T Grey
Aug 8, 2006·Autoimmunity Reviews·Clive H Wasserfall, Mark A Atkinson
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Giselle ChamberlainE Allison Green
Apr 21, 2007·The Journal of Clinical Investigation·Stephanie O HarbersRaphael Clynes
Dec 7, 2007·The Journal of Clinical Investigation·Chang-yun HuLi Wen

❮ Previous
Next ❯

Citations

Apr 11, 2009·Apoptosis : an International Journal on Programmed Cell Death·Aidan RyanFionnuala B Hickey
Jun 27, 2008·Transplantation·David M TarlintonKenneth G C Smith
Jan 1, 2012·The Review of Diabetic Studies : RDS·Kate L GrahamThomas W H Kay
Feb 10, 2010·International Journal of Diabetes in Developing Countries·C B Sanjeevi
Sep 6, 2014·Current Diabetes Reports·Rochelle M Hinman, John C Cambier
Apr 29, 2010·Seminars in Immunopathology·Sarah J RichardsonAlan K Foulis
Jun 24, 2008·Journal of Immunotoxicology·François D DufourAlan G Baxter
May 19, 2010·Expert Review of Clinical Immunology·S Lewis Cox, Pablo A Silveira
May 3, 2011·Trends in Immunology·Eliana MariñoShane T Grey
Nov 6, 2010·Current Opinion in Immunology·F Susan WongLi Wen
Sep 21, 2010·Journal of Autoimmunity·Gwen S ScottF Susan Wong
Oct 14, 2008·Cellular Immunology·Jiezhong Chen, Xiaosong Liu
Jan 9, 2009·Clinical and Experimental Immunology·A WillcoxN G Morgan
Mar 19, 2014·Journal of Cellular and Molecular Medicine·Min LiXin-Yu Qin
Jan 1, 2012·Scientifica·Christiane S Hampe
Jul 28, 2013·International Reviews of Immunology·Kamal D PuriMichael R Gold
Mar 4, 2011·Expert Opinion on Therapeutic Targets·Jayne L ChamberlainLucy Sk Walker
Jul 26, 2012·Diabetes·Eliana MariñoShane T Grey
Nov 13, 2014·Journal of Leukocyte Biology·Börge ArndtJochen Seissler
Jul 1, 2017·Transplantation·Kosuke MasutaniUNKNOWN Japan Academic Consortium of Kidney Transplantation (JACK) Investigators.
Dec 3, 2008·Expert Opinion on Emerging Drugs·Bo Ahrén
Aug 3, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gemma A RyanLucy S K Walker
Jun 23, 2018·Frontiers in Immunology·Ana Isabel PintoE Allison Green
Dec 29, 2020·Clinical and Experimental Immunology·M BattagliaT I Tree
Jul 7, 2021·Annals of the Rheumatic Diseases·Theresa GraalmannUlrich Kalinke

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