Increased T cell glucose uptake reflects acute rejection in lung grafts

D. L. Chen, X. Wang, S. Yamamoto, D. Carpenter, J. T. Engle, W. Li, X. Lin, D. Kreisel, A. S. Krupnick, H. J. Huang, A. E. Gelman

Research output: Contribution to journalArticle

20 Scopus citations

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 languageEnglish
Pages (from-to)2540-2549
Number of pages10
JournalAmerican Journal of Transplantation
Volume13
Issue number10
DOIs
StatePublished - Oct 1 2013

Keywords

  • Allograft rejection
  • PET
  • T cell depletion
  • T lymphocyte activation
  • lung transplantation

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    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. (2013). Increased T cell glucose uptake reflects acute rejection in lung grafts. American Journal of Transplantation, 13(10), 2540-2549. https://doi.org/10.1111/ajt.12389