Abstract
Collagen II (CII)-induced arthritis in DBA/1j mice is mediated by both CII-reactive T cells and anti-CII Ab-producing B cells. To determine the relative role of these processes in the development of arthritis, we specifically eliminated CII-reactive T cells by treating the mice with CII-pulsed syngeneic macrophages that had been transfected with a binary adenovirus system. These macrophages express murine Fas ligand in a doxycycline-inducible manner with autocrine suicide inhibited by concomitant expression of p35. The mice were treated i.v. with four doses of CII-APC-AdFasLp35Tet or a single dose of AdCMVsTACI (5 x 10(9) PFU), or both simultaneously, beginning 2 wk after priming with CII in CFA. Treatment with CII-APC-AdFasLp35Tet alone or in combination with a single dose of AdCMVsTACI prevented the development of CII-induced arthritis and T cell infiltration in the joint. The elimination of T cells was specific in that a normal T cell response was observed on stimulation with OVA after treatment with CII-APC-AdFasLp35Tet. Treatment with AdCMVsTACI alone prevented production of detectable levels of circulating anti-CII autoantibodies and reduced the severity of arthritis but did not prevent its development. These results indicate that the CII-reactive T cells play a crucial role in the development of CII-induced arthritis and that the anti-CII Abs act to enhance the development of CII-induced arthritis.
MeSH terms
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Adenoviridae / genetics
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Administration, Oral
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Animals
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Antigen-Presenting Cells / transplantation
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Apoptosis / genetics
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Apoptosis / immunology
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Arthritis, Experimental / immunology*
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Arthritis, Experimental / pathology
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Arthritis, Experimental / prevention & control*
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Autoantibodies / biosynthesis
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Autocrine Communication / genetics
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Autocrine Communication / immunology
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B-Lymphocytes / immunology*
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Cartilage, Articular / metabolism
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Cartilage, Articular / pathology
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Cell Migration Inhibition
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Collagen Type II / administration & dosage
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Collagen Type II / immunology*
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Cytomegalovirus / genetics
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Down-Regulation / genetics
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Down-Regulation / immunology
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Drug Therapy, Combination
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Fas Ligand Protein
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Female
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Genetic Vectors / administration & dosage
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Genetic Vectors / therapeutic use
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Inhibitor of Apoptosis Proteins
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Lymphocyte Activation* / genetics
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Lymphocyte Depletion* / methods
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Macrophages, Peritoneal / transplantation
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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Membrane Proteins*
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Mice
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Mice, Inbred DBA
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Receptors, Tumor Necrosis Factor / biosynthesis
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / physiology
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Solubility
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / pathology
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Tetracycline Resistance / genetics
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Trans-Activators / genetics
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Transmembrane Activator and CAML Interactor Protein
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Viral Proteins / genetics
Substances
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Autoantibodies
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Collagen Type II
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Fas Ligand Protein
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Fasl protein, mouse
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Inhibitor of Apoptosis Proteins
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Membrane Glycoproteins
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Membrane Proteins
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Receptors, Tumor Necrosis Factor
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Tnfrsf13b protein, mouse
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Trans-Activators
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Transmembrane Activator and CAML Interactor Protein
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Viral Proteins
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inhibitor of apoptosis, Nucleopolyhedrovirus