title: CD4 T Cells but Not Th17 Cells Are Required for Mouse Lung Transplant Obliterative Bronchiolitis.
abstract: Lung transplant survival is limited by obliterative bronchiolitis (OB), but the mechanisms of OB development are unknown. Previous studies in a mouse model of orthotopic lung transplantation suggested a requirement for IL-17. We have used this orthotopic mouse model to investigate the source of IL-17A and the requirement for T cells producing IL-17A. The major sources of IL-17A were CD4(+) T cells and γδ T cells. Depletion of CD4(+) T cells led to a significantly decreased frequency and number of IL-17A(+) lymphocytes and was sufficient to prevent acute rejection and OB. However, mice with STAT3-deficient T cells, which are unable to differentiate into Th17 cells, rejected lung allografts and developed OB similar to control mice. The frequency of IL-17A(+) cells was not decreased in mice with STAT3-deficient T cells due mainly to the presence of IL-17A(+) γδ T cells. Deficiency of γδ T cells also did not affect the development of airway fibrosis. Our data suggest that CD4(+) T cells are required for OB development and expansion of IL-17A responses in the lung, while Th17 and γδ T cells are not absolutely required and may compensate for each other.
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and Department of Microbiology and Immunology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and Department of Microbiology and Immunology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA.
authors.forename: Pawan Kumar
authors.initials: PK
authors.lastname: Gupta
authors.affiliation: Pulmonary and Critical Care Medicine and Center for Immunobiology, Departments of Medicine and Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and Department of Microbiology and Immunology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Wagner
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Oscar
authors.initials: O
authors.lastname: W Cummings
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and Department of Microbiology and Immunology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
authors.affiliation: Pulmonary and Critical Care Medicine and Center for Immunobiology, Departments of Medicine and Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Wilkes
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and Department of Microbiology and Immunology, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Shilling
mesh_terms: D000818:Animals; D001989:Bronchiolitis Obliterans / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology*; D016040:Lung Transplantation; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050796:STAT3 Transcription Factor / Q000502:physiology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: C098680:Il17a protein, mouse; D020381:Interleukin-17; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D007371:Interferon-gamma
keywords: T cell; animal models: murine; basic (laboratory) research/science; biology; bronchiolitis obliterans (BOS); immunobiology; lung (allograft) function/dysfunction; lung transplantation/pulmonology