In vivo kinetics and nonradioactive imaging of rapidly proliferating cells in graft-versus-host disease
| Autor: | William G. Telford, Hellmut Merkle, Francis A. Flomerfelt, Martin J. Lizak, Michael Eckhaus, Rémy Bosselut, Nataliya P. Buxbaum, Ehydel Castro, Liliane M. dos Santos, Yasmine Belkaid, Veena Kapoor, Andrea C. Carpenter, Natella Maglakelidze, Nicolas Bouladoux, Catherine V. Bare, Ronald E. Gress, Brittany Oliver, Gregory Swan, Donald Eugene Farthing |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chemotherapy business.industry Effector Cell growth medicine.medical_treatment General Medicine Hematopoietic stem cell transplantation Disease medicine.disease Molecular biology Transplantation 03 medical and health sciences 030104 developmental biology Graft-versus-host disease Technical Advance immune system diseases Apoptosis hemic and lymphatic diseases medicine Cancer research business |
| Zdroj: | JCI Insight. 2 |
| ISSN: | 2379-3708 |
| Popis: | Hematopoietic stem cell transplantation (HSCT) offers a cure for cancers that are refractory to chemotherapy and radiation. Most HSCT recipients develop chronic graft-versus-host disease (cGVHD), a systemic alloimmune attack on host organs. Diagnosis is based on clinical signs and symptoms, as biopsies are risky. T cells are central to the biology of cGVHD. We found that a low Treg/CD4+ T effector memory (Tem) ratio in circulation, lymphoid, and target organs identified early and established mouse cGVHD. Using deuterated water labeling to measure multicompartment in vivo kinetics of these subsets, we show robust Tem and Treg proliferation in lymphoid and target organs, while Tregs undergo apoptosis in target organs. Since deuterium enrichment into DNA serves as a proxy for cell proliferation, we developed a whole-body clinically relevant deuterium MRI approach to nonradioactively detect cGVHD and potentially allow imaging of other diseases characterized by rapidly proliferating cells. |
| Databáze: | OpenAIRE |
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