| Autor: |
Buxbaum NP; Experimental Transplantation and Immunology Branch, National Cancer Institute., Farthing DE; Experimental Transplantation and Immunology Branch, National Cancer Institute., Maglakelidze N; Experimental Transplantation and Immunology Branch, National Cancer Institute., Lizak M; In Vivo NMR Center, National Institute of Neurological Disorders and Stroke., Merkle H; Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke., Carpenter AC; Laboratory of Immune Cell Biology, National Cancer Institute., Oliver BU; Experimental Transplantation and Immunology Branch, National Cancer Institute., Kapoor V; Experimental Transplantation and Immunology Branch, National Cancer Institute., Castro E; Experimental Transplantation and Immunology Branch, National Cancer Institute., Swan GA; Experimental Transplantation and Immunology Branch, National Cancer Institute., Dos Santos LM; Mucosal Immunology Section, National Institute of Allergy and Infectious Diseases, and., Bouladoux NJ; Mucosal Immunology Section, National Institute of Allergy and Infectious Diseases, and., Bare CV; Experimental Transplantation and Immunology Branch, National Cancer Institute., Flomerfelt FA; Experimental Transplantation and Immunology Branch, National Cancer Institute., Eckhaus MA; Diagnostic and Research Services Branch, Office of the Director, NIH, Bethesda, Maryland, USA., Telford WG; Experimental Transplantation and Immunology Branch, National Cancer Institute., Belkaid Y; Mucosal Immunology Section, National Institute of Allergy and Infectious Diseases, and., Bosselut RJ; Laboratory of Immune Cell Biology, National Cancer Institute., Gress RE; Experimental Transplantation and Immunology Branch, National Cancer Institute. |
| Abstrakt: |
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. |
