Abstract
T cells play a significant role in the pathogenesis of systemic autoimmune diseases, including systemic lupus erythematosus; however, there is relatively little information on the nature and specificity of autoreactive T cells. Identifying such cells has been technically difficult because they are likely to be rare and low affinity. Here, we report a method for identifying autoreactive T cell clones that recognize proteins contained in autoantibody immune complexes, providing direct evidence that functional autoreactive helper T cells exist in the periphery of normal mice. These T cells significantly enhanced autoreactive B cell proliferation and altered B cell differentiation in vivo. Most importantly, these autoreactive T cells were able to rescue many aspects of the TLR-deficient AM14 (anti-IgG2a rheumatoid factor) B cell response, suggesting that TLR requirements can be bypassed. This result has implications for the efficacy of TLR-targeted therapy in the treatment of ongoing disease.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen-Antibody Complex / immunology
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Autoantibodies / immunology
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Autoimmunity / immunology*
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B-Lymphocytes / immunology*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology
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Lymphocyte Activation / immunology*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Mice
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Mice, Knockout
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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Signal Transduction
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T-Lymphocytes, Helper-Inducer / immunology*
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Toll-Like Receptor 7 / genetics
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Toll-Like Receptor 7 / immunology
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Toll-Like Receptor 9 / genetics
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Toll-Like Receptor 9 / immunology
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Toll-Like Receptors / immunology*
Substances
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Antigen-Antibody Complex
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Autoantibodies
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DNA-Binding Proteins
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Membrane Glycoproteins
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Rag2 protein, mouse
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Receptors, Antigen, T-Cell, alpha-beta
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Tlr7 protein, mouse
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Tlr9 protein, mouse
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Toll-Like Receptor 7
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Toll-Like Receptor 9
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Toll-Like Receptors