Instillation of allogeneic lung macrophages and dendritic cells cause differential effects on local IFN-gamma production, lymphocytic bronchitis, and vasculitis in recipient murine lungs

• Published in: Journal of leukocyte biology Vol. 64; no. 5; pp. 578 - 586
• Main Authors: Wilkes, D S, Thompson, L K, Cummings, O W, Bragg, S, Heidler, K M
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.11.1998
• Subjects: AIDS/HIV; Animals; Antigen Presentation; Bronchitis - etiology; Bronchitis - immunology; Bronchitis - pathology; Dendritic Cells - transplantation; Female; Graft Rejection - etiology; Graft Rejection - immunology; Graft Rejection - pathology; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Lung - pathology; Macrophages, Alveolar - transplantation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Th1 Cells - immunology; Th1 Cells - metabolism; Transplantation, Homologous; Vasculitis, Leukocytoclastic, Cutaneous - etiology; Vasculitis, Leukocytoclastic, Cutaneous - immunology; Vasculitis, Leukocytoclastic, Cutaneous - pathology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.64.5.578

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.