title: Peripherally Generated Foxp3+Regulatory T Cells Mediate the Immunomodulatory Effects of IVIg in Allergic Airways Disease.
abstract: IVIg is widely used as an immunomodulatory therapy. We have recently demonstrated that IVIg protects against airway hyperresponsiveness (AHR) and inflammation in mouse models of allergic airways disease (AAD), associated with induction of Foxp3+regulatory T cells (Treg). Using mice carrying aDTR/EGFPtransgene under the control of theFoxp3promoter (DEREG mice), we demonstrate in this study that IVIg generates a de novo population of peripheral Treg (pTreg) in the absence of endogenous Treg. IVIg-generated pTreg were sufficient for inhibition of OVA-induced AHR in an Ag-driven murine model of AAD. In the absence of endogenous Treg, IVIg failed to confer protection against AHR and airway inflammation. Adoptive transfer of purified IVIg-generated pTreg prior to Ag challenge effectively prevented airway inflammation and AHR in an Ag-specific manner. Microarray gene expression profiling of IVIg-generated pTreg revealed upregulation of genes associated with cell cycle, chromatin, cytoskeleton/motility, immunity, and apoptosis. These data demonstrate the importance of Treg in regulating AAD and show that IVIg-generated pTreg are necessary and sufficient for inhibition of allergen-induced AAD. The ability of IVIg to generate pure populations of highly Ag-specific pTreg represents a new avenue to study pTreg, the cross-talk between humoral and cellular immunity, and regulation of the inflammatory response to Ags.
authors.affiliation: Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.|Cellular and Molecular Immunology Laboratory, University of Montreal Hospital Research Centre, Montreal, Quebec H2X 0A9, Canada; and.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Massoud
authors.affiliation: Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
authors.forename: Gabriel N
authors.identifier: 0000-0003-4665-968X
authors.initials: GN
authors.lastname: Kaufman
authors.affiliation: Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
authors.forename: Di
authors.initials: D
authors.lastname: Xue
authors.affiliation: Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
authors.forename: Marianne
authors.identifier: -0000-0003-0264-8540
authors.initials: M
authors.lastname: Béland
authors.affiliation: Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
authors.forename: Marieme
authors.identifier: 0000-0002-4865-7998
authors.initials: M
authors.lastname: Dembele
authors.affiliation: Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
authors.forename: Ciriaco A
authors.initials: CA
authors.lastname: Piccirillo
authors.affiliation: Cellular and Molecular Immunology Laboratory, University of Montreal Hospital Research Centre, Montreal, Quebec H2X 0A9, Canada; and.
authors.forename: Walid
authors.initials: W
authors.lastname: Mourad
authors.affiliation: Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada; bruce.mazer@mcgill.ca.
authors.forename: Bruce D
authors.identifier: 0000-0003-4018-1419
authors.initials: BD
authors.lastname: Mazer
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D059467:Transcriptome
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016756:Immunoglobulins, Intravenous