Abstract
Previous studies attempting to influence the severity of collagen-induced arthritis (CIA) by modulating the LIGHT (lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator (HVEM) on T cells)/lymphotoxin pathway have yielded conflicting results. To further clarify the role of LIGHT in autoimmune arthritis, a HVEM-Ig fusion protein was used. CIA was induced in DBA1 mice, which were injected i.p. with recombinant HVEM-Ig fusion protein and control Ig at different time points. Severity of clinical arthritis and histologic joint destruction were significantly increased in HVEM-Ig-treated mice compared with control-Ig-treated mice. Collagen II-induced in vitro T cell proliferation and IFN-gamma production was augmented in mice treated with HVEM-Ig, as was the production of IgG2a anti-collagen II Ab. Accordingly, serum concentrations of IFN-gamma and IL-6 were higher in mice treated with HVEM-Ig. In conclusion, HVEM-Ig aggravates autoimmunity in collagen-induced arthritis, which is possibly mediated by interaction with B and T lymphocyte attenuator (BTLA) or CD160, despite the blockade of LIGHT. Hence, HVEM-Ig seems not to be a valid therapeutic option in autoimmune arthritis.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Arthritis, Experimental / immunology*
-
Arthritis, Experimental / pathology
-
Arthritis, Rheumatoid / immunology*
-
Arthritis, Rheumatoid / pathology
-
Autoantibodies / biosynthesis
-
CD4-Positive T-Lymphocytes / immunology
-
CD4-Positive T-Lymphocytes / metabolism
-
Collagen Type II / immunology
-
Disease Models, Animal
-
Herpesvirus 1, Human / immunology*
-
Humans
-
Immunoglobulin Fc Fragments / administration & dosage*
-
Immunoglobulin Fc Fragments / genetics
-
Lymphotoxin beta Receptor / administration & dosage
-
Lymphotoxin beta Receptor / genetics
-
Lymphotoxin beta Receptor / immunology
-
Mice
-
Mice, Inbred DBA
-
Receptors, Immunologic / administration & dosage
-
Receptors, Immunologic / genetics
-
Receptors, Immunologic / immunology
-
Receptors, Tumor Necrosis Factor, Member 14 / administration & dosage
-
Receptors, Tumor Necrosis Factor, Member 14 / genetics
-
Receptors, Tumor Necrosis Factor, Member 14 / immunology*
-
Recombinant Fusion Proteins / administration & dosage
-
Recombinant Fusion Proteins / immunology
-
Tumor Necrosis Factor Ligand Superfamily Member 14 / administration & dosage
-
Tumor Necrosis Factor Ligand Superfamily Member 14 / antagonists & inhibitors
-
Tumor Necrosis Factor Ligand Superfamily Member 14 / immunology
Substances
-
Autoantibodies
-
BTLA protein, mouse
-
Collagen Type II
-
Immunoglobulin Fc Fragments
-
Lymphotoxin beta Receptor
-
Receptors, Immunologic
-
Receptors, Tumor Necrosis Factor, Member 14
-
Recombinant Fusion Proteins
-
Tumor Necrosis Factor Ligand Superfamily Member 14