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Increased T Cell Glucose Uptake Reflects Acute Rejection in Lung Grafts
Author(s) -
Chen D. L.,
Wang X.,
Yamamoto S.,
Carpenter D.,
Engle J. T.,
Li W.,
Lin X.,
Kreisel D.,
Krupnick A. S.,
Huang H. J.,
Gelman A. E.
Publication year - 2013
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.12389
Subject(s) - medicine , immunosuppression , lung , deoxyglucose , cd8 , transplantation , pathology , lung transplantation , glucose uptake , positron emission tomography , antigen , immunology , nuclear medicine , insulin
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 [ 18 F]fluorodeoxyglucose ([ 18 F]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 [ 18 F]FDG uptake in rejecting allografts when compared to transplanted lungs of either immunosuppressed or syngeneic recipients. [ 18 F]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.