Buxbaum Nataliya P, Farthing Donald E, Maglakelidze Natella, Lizak Martin, Merkle Hellmut, Carpenter Andrea C, Oliver Brittany U, Kapoor Veena, Castro Ehydel, Swan Gregory A, Dos Santos Liliane M, Bouladoux Nicolas J, Bare Catherine V, Flomerfelt Francis A, Eckhaus Michael A, Telford William G, Belkaid Yasmine, Bosselut Remy J, Gress Ronald E
Experimental Transplantation and Immunology Branch, National Cancer Institute.
In Vivo NMR Center, National Institute of Neurological Disorders and Stroke.
JCI Insight. 2017 Jun 15;2(12). doi: 10.1172/jci.insight.92851.
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.
造血干细胞移植（HSCT）为化疗和放疗难治的癌症提供了治愈方法。大多数接受HSCT的患者会发生慢性移植物抗宿主病（cGVHD），这是一种针对宿主器官的全身性同种免疫攻击。由于活检存在风险，诊断基于临床体征和症状。T细胞在cGVHD生物学中起核心作用。我们发现，循环、淋巴和靶器官中低调节性T细胞（Treg）/CD4+效应记忆T细胞（Tem）比值可识别早期和已确诊的小鼠cGVHD。使用氘水标记来测量这些亚群的多室体内动力学，我们发现淋巴和靶器官中Tem和Treg有强劲增殖，而Treg在靶器官中发生凋亡。由于氘掺入DNA可作为细胞增殖的指标，我们开发了一种全身临床相关的氘磁共振成像方法，以非放射性方式检测cGVHD，并有可能对其他以细胞快速增殖为特征的疾病进行成像。
