Prevention of chronic graft-versus-host disease by stimulation with glucocorticoid-induced TNF receptor.
- Author:
Juyang KIM
1
;
Woon Sun CHOI
;
Hye Jeong KIM
;
Byungsuk KWON
Author Information
1. The Immunomodulation Research Center and Department of Biological Science, University of Ulsan, Ulsan 680-749, Korea. bkwon@mail.ulsan.ac.kr
- Publication Type:Original Article ; Comparative Study ; Research Support, Non-U.S. Gov't
- Keywords:
autoantibodies;
B-lymphocytes;
glomerulonephritis;
graft vs host disease;
immunotherapy;
TNFRSF18 protein;
mouse
- MeSH:
Animals;
Antibodies, Monoclonal/therapeutic use;
B-Lymphocytes/immunology;
CD4-Positive T-Lymphocytes/drug effects/immunology/transplantation;
Comparative Study;
Enzyme-Linked Immunosorbent Assay;
Female;
Flow Cytometry;
Fluorescein-5-isothiocyanate;
Fluorescent Antibody Technique, Indirect;
Fluorescent Dyes;
Glucocorticoids/*pharmacology;
Graft vs Host Disease/*prevention & control;
Mice;
Mice, Inbred DBA;
Mice, Inbred Strains;
Microscopy, Confocal;
Receptors, Tumor Necrosis Factor/*immunology;
Research Support, Non-U.S. Gov't;
Transplantation, Homologous
- From:Experimental & Molecular Medicine
2006;38(1):94-99
- CountryRepublic of Korea
- Language:English
-
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.
