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Mononuclear phagocyte populations in the transplanted human lung
D S Milne1, A D Gascoigne, J Coaker
1University Department of Pathology, Royal Victoria Infirmary, Newcastle-upon-Tyne, United Kingdom.
Insights
Lung transplantation leads to a significant decrease in dendritic cells (DC) and altered alveolar macrophages. These changes, particularly macrophage alterations, may reverse during acute rejection, highlighting the need for further research.
Area of Science:
- Immunology
- Transplantation Science
- Pulmonary Medicine
Background:
- Dendritic cells (DC) are critical for immune responses in alloreactivity.
- Limited data exists on DC and mononuclear cell distribution in human lung transplants.
Purpose of the Study:
- To investigate the distribution and phenotype of dendritic cells (DC) and related mononuclear cells in human lung allografts.
- To assess the impact of lung transplantation and immunosuppression on these cell populations.
Main Methods:
- Analysis of frozen lung sections from transplant recipients and donor lungs.
- Immunohistochemical examination for CD1a+ DC, CD11b, and CD68 expression on mononuclear cells and alveolar macrophages.
- Comparison of biopsy specimens from normal allografts, rejection, and obliterative bronchiolitis.
Main Results:
- A significant depletion of CD1a+ dendritic cells (DC) was observed in all lung allografts, including those with obliterative bronchiolitis.
- Transplantation and immunosuppression reduced coexpression of CD68 and CD11b on alveolar macrophages.
- This reduction in macrophage markers was reversed in cases of acute rejection.
Conclusions:
- Pulmonary dendritic cell (DC) roles and other mononuclear phagocyte functions require further elucidation in lung transplantation.
- Findings from animal models of lung transplantation should be interpreted cautiously due to potential species-specific differences.
Background:
Dendritic cells (DC) are essential for the development of alloreactivity, however, little has been published regarding the distribution and phenotype of these and related mononuclear cells in human lung transplantation.
Methods:
Lung frozen sections were examined for the presence of CD1a+ DC and for mononuclear cells and alveolar macrophages expressing CD11b and CD68. The effects of transplantation and immunosuppression were assessed by comparison of normal transplant transbronchial biopsy specimens to specimens from unused donor lungs; the normal transbronchial biopsy specimens also were compared with those showing rejection or obliterative bronchiolitis.
Results:
All biopsy specimens, including those with obliterative bronchiolitis, showed a marked depletion of CD1a+ DC in lung allografts. This has not been described previously. In addition, transplantation and immunosuppression reduced alveolar macrophage coexpression of CD68 and CD11b, and this was reversed in acute rejection.
Conclusion:
The roles of pulmonary DC and other mononuclear phagocyte subpopulations need to be further defined, and data from animal models of lung transplantation should be interpreted with caution.