title: The Escherichia coli heat-labile enterotoxin B subunit protects from allergic airway disease development by inducing CD4+ regulatory T cells.
abstract: The B subunit of E. coli heat-labile enterotoxin (EtxB) protects against the development of T helper type 1 (Th1)-mediated autoimmune pathologies in mice. Protection was transferable with splenic CD4(+) T cells and was less effective following CD25 depletion; implying a T regulatory cell (Treg)-mediated process. We hypothesized that if this were the case, then EtxB would also control a Th2-mediated disorder. We tested the effect of EtxB treatment on asthma development in ovalbumin (OVA)-sensitized mice. EtxB treatment diminished eosinophilia in bronchoalveolar lavage samples, reduced OVA-specific immunoglobulin E and interleukin 4 production locally and systemically, and reduced airway hyper-reactivity. EtxB induced a dose-dependent increase in Foxp3(+)CD4(+) T cells, and adoptive transfer of splenic CD4(+) T cells partially suppressed lung pathology. Importantly, EtxB treatment increased OVA-specific CD4(+)Foxp3(+) T cells in the lung and systemically. These data demonstrate that EtxB modulates the differentiation of allergen-specific T cells causing inducible Treg induction and preventing disease.
authors.affiliation: Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, UK.
authors.forename: D S
authors.initials: DS
authors.lastname: Donaldson
authors.forename: M
authors.initials: M
authors.lastname: Apostolaki
authors.forename: H K
authors.initials: HK
authors.lastname: Bone
authors.forename: C M
authors.initials: CM
authors.lastname: Richards
authors.forename: N A
authors.initials: NA
authors.lastname: Williams
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000517:prevention & control*; D001327:Autoimmune Diseases / Q000517:prevention & control*; D001427:Bacterial Toxins / Q000008:administration & dosage*; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D004768:Enterotoxins / Q000008:administration & dosage*; D004804:Eosinophils / Q000276:immunology; D029968:Escherichia coli Proteins / Q000008:administration & dosage*; D005260:Female; D056724:Immunity, Humoral; D007073:Immunoglobulin E / Q000097:blood; D007165:Immunosuppression Therapy; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D001427:Bacterial Toxins; D015704:CD4 Antigens; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin; C027538:heat-labile enterotoxin, E coli