Instillation of allogeneic lung macrophages and dendritic cells cause differential effects on local IFN-gamma production, lymphocytic bronchitis, and vasculitis in recipient murine lungs.
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.
Wilkes
D S
DS
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA. dwilkes@mdep.iupui.edu
Thompson
L K
LK
Cummings
O W
OW
Bragg
S
S
Heidler
K M
KM
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
D007371:Interferon-gamma