title: Instillation of allogeneic lung macrophages and dendritic cells cause differential effects on local IFN-gamma production, lymphocytic bronchitis, and vasculitis in recipient murine lungs.
abstract: Lung allograft rejection is believed to be initiated by donor lung accessory cells, namely macrophages and dendritic cells, interacting with recipient lymphocytes leading to up-regulated Th1 type (IFN-gamma) cellular immunity culminating in graft destruction. The purpose of this study was to determine the individual role of donor lung macrophages and dendritic cells in the rejection response. Utilizing a murine model that reproduces the immunology and histology of acute rejection, C57BL/6 mouse (I-a(b), H-2(b)) lung dendritic cells (DC-enriched lung cells), purified alveolar macrophages (I-a-negative macrophages), or various ratios of I-a-negative macrophages/DC were instilled into BALB/c mouse (I-a(d), H-2(d)) lungs followed by an assessment of local IFN-gamma production and grading of rejection pathology. The data show that DC, and not I-a-negative macrophages, induced IFN-gamma production in recipient lungs. However, the local production of IFN-gamma was not always associated with histological changes characteristic of rejection pathology. In contrast to either cell type alone, instillation of C57BL/6 I-a-negative macrophages and DC, together, were required to induce rejection pathology in BALB/c lungs. In addition, the rejection response was dependent on interactions between donor I-a-negative macrophages and DC.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA. dwilkes@mdep.iupui.edu
authors.forename: D S
authors.initials: DS
authors.lastname: Wilkes
authors.forename: L K
authors.initials: LK
authors.lastname: Thompson
authors.forename: O W
authors.initials: OW
authors.lastname: Cummings
authors.forename: S
authors.initials: S
authors.lastname: Bragg
authors.forename: K M
authors.initials: KM
authors.lastname: Heidler
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001991:Bronchitis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000637:transplantation*; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000637:transplantation*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous; D018366:Vasculitis, Leukocytoclastic, Cutaneous / Q000209:etiology* / Q000276:immunology / Q000473:pathology
chemical_list: D007371:Interferon-gamma