Abstract
Although T cells are required for acute lung rejection, other graft-infiltrating cells such as neutrophils accumulate in allografts and are also high glucose utilizers. Positron emission tomography (PET) with the glucose probe [18F]fluorodeoxyglucose ([18F]FDG) has been employed to image solid organ acute rejection, but the sources of glucose utilization remain undefined. Using a mouse model of orthotopic lung transplantation, we analyzed glucose probe uptake in the grafts of syngeneic and allogeneic recipients with or without immunosuppression treatment. Pulmonary microPET scans demonstrated significantly higher [18F]FDG uptake in rejecting allografts when compared to transplanted lungs of either immunosuppressed or syngeneic recipients. [18F]FDG uptake was also markedly attenuated following T cell depletion therapy in lung recipients with ongoing acute rejection. Flow cytometric analysis using the fluorescent deoxyglucose analog 2-NBDG revealed that T cells, and in particular CD8 + T cells, were the largest glucose utilizers in acutely rejecting lung grafts followed by neutrophils and antigen-presenting cells. These data indicate that imaging modalities tailored toward assessing T cell metabolism may be useful in identifying acute rejection in lung recipients. Positron emission tomography in combination with flow cytometric analysis reveals that graft resident T cells drive glucose utilization in acutely rejecting mouse lungs.
Original language | English |
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Pages (from-to) | 2540-2549 |
Number of pages | 10 |
Journal | American Journal of Transplantation |
Volume | 13 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2013 |
Keywords
- Allograft rejection
- PET
- T cell depletion
- T lymphocyte activation
- lung transplantation