Abstract
Mechanisms that control abnormal CD4(+) T cell-mediated tissue damage are a significant factor in averting and resolving chronic inflammatory epithelial diseases. B cells can promote such immunoregulation, and this is thought to involve interaction with MHC II- or CD1-restricted regulatory T cells. The purpose of this study is to genetically define the interacting cells targeted by protective B cells, and to elucidate their regulatory mechanisms in CD4(+) T cell inflammation. Transfer of G alpha i2-/- CD3(+) T cells into lymphopenic mice causes a dose-dependent multi-organ inflammatory disease including the skin, intestine, and lungs. Disease activity is associated with elevated levels of serum TNF-alpha and IFN-gamma, and an activated IL-17 producing CD4(+) T cell population. Mesenteric node B cells from wild type mice suppress disease activity, serum cytokine expression, and levels of CD4(+) T cells producing TNF-alpha IFN-gamma, and IL-17. The protective function of B cells requires genetic sufficiency of IL-10, MHC I and TAP1. Regulatory B cells induce the expansion and activation of CD8(+) T cells, which is correlated with disease protection. These results demonstrate that CD8(+) T cells can ameliorate lymphopenic systemic inflammatory disease, through peptide/MHC I-dependent B cell interaction.
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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ATP Binding Cassette Transporter, Subfamily B, Member 2
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ATP-Binding Cassette Transporters / immunology
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ATP-Binding Cassette Transporters / metabolism
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Animals
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Communication
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Epithelium / immunology*
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Epithelium / metabolism
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GTP-Binding Proteins / metabolism
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class I / metabolism
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Inflammation / immunology*
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Inflammation / metabolism
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Interleukin-10 / immunology
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Interleukin-10 / metabolism
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Lymphocyte Activation
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Mice
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Mice, Mutant Strains
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 2
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ATP-Binding Cassette Transporters
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Histocompatibility Antigens Class I
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Tap1 protein, mouse
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Tumor Necrosis Factor-alpha
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Interleukin-10
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Interferon-gamma
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GTP-Binding Proteins