Exp Mol Med.  2006 Feb;38(1):94-99.

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

• Kim J
• Choi WS
• Kim HJ
• Kwon B

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.

Keyword

autoantibodies; B-lymphocytes; glomerulonephritis; graft vs host disease; immunotherapy; TNFRSF18 protein; mouse

MeSH Terms

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