Prevention of chronic graft-versus-host disease by stimulation with glucocorticoid-induced TNF receptor.
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.
Kim
Juyang
J
The Immunomodulation Research Center and Department of Biological Science, University of Ulsan, Ulsan 680-749, Korea.
Choi
Woon Sun
WS
Kim
Hye Jeong
HJ
Kwon
Byungsuk
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000637:transplantation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D005938:Glucocorticoids / Q000494:pharmacology*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D005456:Fluorescent Dyes; D005938:Glucocorticoids; D018124:Receptors, Tumor Necrosis Factor; D016650:Fluorescein-5-isothiocyanate