Prevention of chronic graft-versus-host disease by stimulation with glucocorticoid-induced TNF receptor

Experimental & Molecular Medicine
Juyang KimByungsuk Kwon

Abstract

GITR (glucocorticoid-induced TNF receptor) is a recently identified member of the TNF receptor superfamily. The receptor is preferentially expressed on CD4+CD25+ regulatory T cells and GITR signals break the suppressive activity of the subset. In this study, we wanted to reveal the in vivo function of GITR in chronic graft-versus-host disease (cGVHD), a lupus-like autoimmune disease. A single injection of anti-GITR monoclonal antibody (DTA-1) was effective in blocking the progression of cGVHD in the parent-into-F1 model. Treatment of DTA-1 significantly decreased levels of IgG1 anti-DNA autoantibody, inhibited glomerulonephritis, and increased survival. The DTA-1-mediated inhibition of autoantibody production correlated with deletion of B cells and could occur independently of CD4+CD25+ regulatory T cells. Our results indicate that anti-GITR monoclonal antibody may be used as a potential immunotherapeutic agent for preventing cGVHD.

Citations

Jul 2, 2010·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Jun-qiang LvZhi Yao
Nov 21, 2009·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Hong ZhouRobert Chunhua Zhao
Apr 30, 2008·Teaching and Learning in Medicine·Erle C H Lim, Raymond C S Seet
Jun 30, 2018·Physiotherapy Theory and Practice·Sue MurphyBetsabeh Parsa
Aug 8, 2008·Current Opinion in Organ Transplantation·Avinash Agarwal, Kenneth A Newell

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