Abstract
In this study, we investigated the effect of an agonistic mAb (DTA-1) against glucocorticoid-induced TNF receptor (GITR) in a murine model of systemic lupus erythematosus-like chronic graft-vs-host disease (cGVHD). A single dose of DTA-1 inhibited the production of anti-DNA IgG1 autoantibody and the development of glomerulonephritis, typical symptoms of cGVHD. DTA-1-treated mice showed clinical and pathological signs of acute GVHD (aGVHD), such as lymphopenia, loss of body weight, increase of donor cell engraftment, and intestinal damage, indicating that DTA-1 shifted cGVHD toward aGVHD. The conversion of cGVHD to aGVHD occurred because DTA-1 prevented donor CD8+ T cell anergy. Functionally active donor CD8+ T cells produced high levels of IFN-gamma and had an elevated CTL activity against host Ags. In in vitro MLR, anergic responder CD8+ T cells were generated, and DTA-1 stimulated the activation of these anergic CD8+ T cells. We further confirmed in vivo that donor CD8+ T cells, but not donor CD4+ T cells, were responsible for the DTA-1-mediated conversion of cGVHD to aGVHD. These results indicate that donor CD8+ T cell anergy is a restriction factor in the development of aGVHD and that in vivo ligation of GITR prevents CD8+ ...Continue Reading
References
Jul 1, 1991·Immunology Today·M GoldmanE Gleichmann
Feb 1, 1990·The Journal of Experimental Medicine·S C MorrisR A Eisenberg
Mar 1, 1983·European Journal of Immunology·A G RolinkE Gleichmann
Nov 1, 1993·The Journal of Experimental Medicine·V A BoussiotisL M Nadler
Jun 1, 1993·International Immunology·C S Via, F D Finkelman
May 1, 1996·The Journal of Experimental Medicine·L ZhangJ Zhang
Jul 8, 1999·Nature Medicine·E M SotomayorH I Levitsky
Jul 31, 1999·Transplantation·B DeyM Sykes
Sep 21, 2000·The Journal of Clinical Investigation·W J Murphy
Sep 21, 2000·The Journal of Clinical Investigation·A ShustovC S Via
Aug 2, 2001·Nature Medicine·P Bansal-PakalaM Croft
Jan 29, 2002·Nature Immunology·Jun ShimizuShimon Sakaguchi
Feb 6, 2002·European Journal of Immunology·David CooperMichael Croft
Mar 1, 2002·Immunity·Rebecca S McHughMichael C Byrne
Nov 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mercedes GonzalezRandolph J Noelle
Sep 13, 2003·Blood·Ryan A WilcoxLieping Chen
Nov 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Masahide ToneHerman Waldmann
Mar 3, 2004·European Journal of Immunology·Simona RonchettiCarlo Riccardi
Apr 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adam P KohmStephen D Miller
May 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hong-bin JiCox Terhorst
May 20, 2004·Blood·Britt E AndersonMark J Shlomchik
Jun 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fumiko KanamaruMiyuki Azuma
Jul 14, 2004·The Journal of Experimental Medicine·Stephanie J MuriglanMarcel R M Van Den Brink
Nov 4, 2004·Blood·Juyang KimByungsuk Kwon
Mar 23, 2005·Immunity·William L Redmond, Linda A Sherman
Citations
Sep 8, 2010·Experimental & Molecular Medicine·Byungsuk Kwon
Feb 4, 2014·Cytokine & Growth Factor Reviews·Derek L Clouthier, Tania H Watts
Oct 5, 2010·Immunology Letters·Simona RonchettiCarlo Riccardi
Apr 7, 2010·Trends in Immunology·Charles S Via
Oct 1, 2011·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Juyang KimByungsuk Kwon
Feb 11, 2009·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Wonyoung KimByungsuk Kwon
Apr 24, 2016·The American Journal of Pathology·Jie MaShengjun Wang
Mar 5, 2015·PLoS Pathogens·Maria Fernanda PascuttiMartijn A Nolte
Apr 22, 2016·Clinical Rheumatology·Linbo LiZhanguo Li
Mar 17, 2007·Blood·Juyang KimByungsuk Kwon
Oct 12, 2010·Clinical & Developmental Immunology·Theresa PlackeHelmut Rainer Salih
Jun 2, 2012·TheScientificWorldJournal·Simona RonchettiCarlo Riccardi
Oct 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Simona RonchettiCarlo Riccardi
Aug 15, 2018·Expert Opinion on Therapeutic Targets·Carlo RiccardiGiuseppe Nocentini
Nov 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Juyang KimByungsuk Kwon
Jun 10, 2010·Immune Network·Juyang KimByungsuk Kwon
Jun 6, 2009·Cancer Gene Therapy·D BoczkowskiS Nair