Abstract
We recently reported on an inflammatory arthropathy resembling rheumatoid arthritis that develops in high incidence among transgenic mice that carry the env-pX region of the human T cell leukemia virus type 1 genome. In an effort to elucidate the pathogenesis of this disease, we found that genes for inflammatory cytokines, including IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, transforming growth factor-beta 1, IFN-gamma, and IL-2, as well as MHC genes were activated in transgenic joints. Serum levels of IL-1 beta and IL-6 were also elevated. Interestingly, these mice produced Ab against IgG, type II collagen (IIC), and heat shock proteins accompanied by IgG hypergammaglobulinemia. The cellular immune response to IIC as well as that to heat shock proteins were activated. Moreover, these mice became immunologically responsive to exogenously administered IIC and developed arthritis, in contrast to their nontransgenic littermates, which showed little response to IIC. Taken together, the results suggest that human T cell leukemia virus type 1 can cause immune system hyperreactivity and induce autoimmunity. The possibility that elevated cytokine and/or MHC gene expression are involved in the development of autoimmunity and arthropathy are discussed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Anti-Idiotypic / biosynthesis
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Antibodies, Anti-Idiotypic / immunology
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Arthritis, Rheumatoid / blood
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Arthritis, Rheumatoid / immunology
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Arthritis, Rheumatoid / pathology
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Arthritis, Rheumatoid / virology*
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Autoantibodies / biosynthesis
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Autoantibodies / immunology*
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Autoantigens / immunology*
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Autoimmune Diseases / blood
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Autoimmune Diseases / immunology
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Autoimmune Diseases / pathology
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Autoimmune Diseases / virology*
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Collagen / immunology*
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Cytokines / biosynthesis*
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Cytokines / blood
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Cytokines / genetics
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Disease Models, Animal*
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Female
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Gene Expression Regulation, Viral*
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Gene Products, tax / genetics
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Gene Products, tax / physiology*
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Genes, env
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Genes, pX
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H-2 Antigens / biosynthesis
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H-2 Antigens / genetics
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HTLV-I Infections / immunology*
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Heat-Shock Proteins / immunology*
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Histocompatibility Antigens Class II / biosynthesis
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Histocompatibility Antigens Class II / genetics
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Human T-lymphotropic virus 1 / genetics*
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Humans
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Hypergammaglobulinemia / immunology
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Hypergammaglobulinemia / virology*
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Immunoglobulin G / immunology*
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Interleukins / biosynthesis
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Interleukins / blood
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Interleukins / genetics
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Transgenic
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Severity of Illness Index
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Tumor Necrosis Factor-alpha / analysis
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / genetics
Substances
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Antibodies, Anti-Idiotypic
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Autoantibodies
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Autoantigens
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Cytokines
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Gene Products, tax
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H-2 Antigens
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Heat-Shock Proteins
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Histocompatibility Antigens Class II
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I-E-antigen
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Immunoglobulin G
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Interleukins
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Tumor Necrosis Factor-alpha
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Collagen