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

David S. Wilkes, Linda K. Thompson, Oscar W. Cummings, Shanda Bragg, Kathleen M. Heidler

Research output: Contribution to journalArticle

13 Scopus citations

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-γ) 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-γ production and grading of rejection pathology. The data show that DC, and not I-a-negative macrophages, induced IFN-γ production in recipient lungs. However, the local production of IFN-γ 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.

Original languageEnglish (US)
Pages (from-to)578-586
Number of pages9
JournalJournal of Leukocyte Biology
Volume64
Issue number5
DOIs
StatePublished - Nov 1998

Keywords

  • Allograft rejection
  • BALB/c mouse
  • C57BL/6 mouse

ASJC Scopus subject areas

  • Cell Biology

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