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

被引：16

作者：

Buxbaum, Nataliya P. ^{[1
]}

Farthing, Donald E. ^{[1
]}

Maglakelidze, Natella ^{[1
]}

Lizak, Martin ^{[2
]}

Merkle, Hellmut ^{[3
]}

Carpenter, Andrea C. ^{[4
]}

Oliver, Brittany U. ^{[1
]}

Kapoor, Veena ^{[1
]}

Castro, Ehydel ^{[1
]}

Swan, Gregory A. ^{[1
]}

dos Santos, Liliane M. ^{[5
]}

Bouladoux, Nicolas J. ^{[5
]}

Bare, Catherine V. ^{[1
]}

Flomerfelt, Francis A. ^{[1
]}

Eckhaus, Michael A. ^{[6
]}

Telford, William G. ^{[1
]}

Belkaid, Yasmine ^{[5
]}

Bosselut, Remy J. ^{[4
]}

Gress, Ronald E. ^{[1
]}

机构：

[1] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA

[2] NINDS, In Vivo NMR Ctr, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

[3] NINDS, Lab Funct & Mol Imaging, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

[4] NCI, Lab Immune Cell Biol, Bethesda, MD 20892 USA

[5] NIAID, Mucosal Immunol Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA

[6] NIH, Diagnost & Res Serv Branch, Off Director, Bldg 10, Bethesda, MD 20892 USA

来源：

JCI INSIGHT | 2017年 / 2卷 / 12期

关键词：

REGULATORY T-CELLS; CONSENSUS DEVELOPMENT PROJECT; CLINICAL-TRIALS; DE-NOVO; IMMUNITY; DNA; INTERLEUKIN-2; LYMPHOCYTES; DIAGNOSIS; RESPONSES;

D O I：

10.1172/jci.insight.92851

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页数：17

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