title: Integration of B cells and CD8+ T in the protective regulation of systemic epithelial inflammation.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095-1732, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Wei
authors.forename: Michael
authors.initials: M
authors.lastname: McPherson
authors.forename: Olga
authors.initials: O
authors.lastname: Turovskaya
authors.forename: Peter
authors.initials: P
authors.lastname: Velazquez
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujiwara
authors.forename: Sarah
authors.initials: S
authors.lastname: Brewer
authors.forename: Jonathan
authors.initials: J
authors.lastname: Braun
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication; D004848:Epithelium / Q000276:immunology* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C486171:Tap1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D019204:GTP-Binding Proteins