In vivo kinetics and nonradioactive imaging of rapidly proliferating cells in graft-versus-host disease

Nataliya P Buxbaum; Donald E Farthing; Natella Maglakelidze; Martin Lizak; Hellmut Merkle; Andrea C Carpenter; Brittany U Oliver; Veena Kapoor; Ehydel Castro; Gregory A Swan; Liliane M Dos Santos; Nicolas J Bouladoux; Catherine V Bare; Francis A Flomerfelt; Michael A Eckhaus; William G Telford; Yasmine Belkaid; Remy J Bosselut; Ronald E Gress

doi:10.1172/jci.insight.92851

In vivo kinetics and nonradioactive imaging of rapidly proliferating cells in graft-versus-host disease

JCI Insight. 2017 Jun 15;2(12):e92851. doi: 10.1172/jci.insight.92851.

Authors

Nataliya P Buxbaum¹, Donald E Farthing¹, Natella Maglakelidze¹, Martin Lizak², Hellmut Merkle³, Andrea C Carpenter⁴, Brittany U Oliver¹, Veena Kapoor¹, Ehydel Castro¹, Gregory A Swan¹, Liliane M Dos Santos⁵, Nicolas J Bouladoux⁵, Catherine V Bare¹, Francis A Flomerfelt¹, Michael A Eckhaus⁶, William G Telford¹, Yasmine Belkaid⁵, Remy J Bosselut⁴, Ronald E Gress¹

Affiliations

¹ Experimental Transplantation and Immunology Branch, National Cancer Institute.
² In Vivo NMR Center, National Institute of Neurological Disorders and Stroke.
³ Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke.
⁴ Laboratory of Immune Cell Biology, National Cancer Institute.
⁵ Mucosal Immunology Section, National Institute of Allergy and Infectious Diseases, and.
⁶ Diagnostic and Research Services Branch, Office of the Director, NIH, Bethesda, Maryland, USA.

Abstract

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.

Keywords: Immunology; Transplantation.