Increased T cell glucose uptake reflects acute rejection in lung grafts.
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.
Division of Radiological Sciences and Nuclear Medicine, Department of Radiology, Washington University School of Medicine, St. Louis, MO.
D L
DL
Chen
X
X
Wang
S
S
Yamamoto
D
D
Carpenter
J T
JT
Engle
W
W
Li
X
X
Lin
D
D
Kreisel
A S
AS
Krupnick
H J
HJ
Huang
A E
AE
Gelman
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D019788:Fluorodeoxyglucose F18; D006084:Graft Rejection / Q000000981:diagnostic imaging* / Q000209:etiology / Q000276:immunology; D007091:Image Processing, Computer-Assisted; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016040:Lung Transplantation; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D007166:Immunosuppressive Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
Allograft rejection; PET; T cell depletion; T lymphocyte activation; lung transplantation