Conversion of alloantigen-specific CD8+ T cell anergy to CD8+ T cell priming through in vivo ligation of glucocorticoid-induced TNF receptor

The Journal of Immunology : Official Journal of the American Association of Immunologists
Juyang KimByungsuk Kwon

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

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Citations

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
Mar 5, 2015·PLoS Pathogens·Maria Fernanda PascuttiMartijn A Nolte
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

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