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在实验性 1 型糖尿病模型中,过继转移的自身反应性 T 淋巴细胞的标记和纵向跟踪面临的挑战。

Challenges for labeling and longitudinal tracking of adoptively transferred autoreactive T lymphocytes in an experimental type-1 diabetes model.

机构信息

Biomedical MRI/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.

Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium.

出版信息

MAGMA. 2019 Jun;32(3):295-305. doi: 10.1007/s10334-018-0720-x. Epub 2019 Jan 16.

Abstract

OBJECTIVE

Tracking the autoreactive T-cell migration in the pancreatic region after labeling with fluorinated nanoparticles (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[3-(2-pyridyldithio)propionate]-perfluoro-15-crown-5-ether nanoparticles, PDP-PFCE NPs) in a diabetic murine model using F MRI.

MATERIALS AND METHODS

Synthesis of novel PDP-PFCE fluorine tracer was performed for in vitro labeling of T cells. Labeling conditions were optimized using different PDP-PFCE NPs concentrations. For in vivo F MRI, mice were longitudinally followed after adoptive transfer of activated, autoreactive, labeled T cells in NOD.SCID mice.

RESULTS

Established MR protocols were used for challenging T cell labeling to track inflammation in a model of diabetes after successful labeling of CD4+ and CD8+ T cells with PDP-PFCE NPs. However, T cells were difficult to be detected in vivo after their engraftment in animals.

DISCUSSION

We showed successful in vitro labeling of T cells using novel fluorinated liposomal nanoparticles. However, insufficient and slow accumulation of labeled T cells and subsequent T cell proliferation in the pancreatic region remains as limitations of in vivo cell imaging by F MRI.

摘要

目的

使用 F MRI 追踪糖尿病鼠模型中经氟化物纳米颗粒(1,2-二油酰基-sn-甘油-3-磷酸乙醇胺-N-[3-(2-吡啶基二硫代)丙酸盐]-全氟-15-冠醚-5-醚纳米颗粒,PDP-PFCE NPs)标记后,在胰腺区域中自身反应性 T 细胞的迁移情况。

材料和方法

合成了新型 PDP-PFCE 氟化物示踪剂,用于体外 T 细胞标记。使用不同的 PDP-PFCE NPs 浓度优化了标记条件。在体内 F MRI 方面,在 NOD.SCID 小鼠中过继转移激活的、自身反应性的、标记的 T 细胞后,对小鼠进行了纵向随访。

结果

成功建立了 MR 方案,用于挑战 T 细胞标记,以在糖尿病模型中追踪炎症,使用 PDP-PFCE NPs 成功标记了 CD4+和 CD8+T 细胞。然而,在动物体内移植后,T 细胞难以被体内检测到。

讨论

我们展示了使用新型氟脂质体纳米颗粒成功地对 T 细胞进行了体外标记。然而,标记的 T 细胞在胰腺区域的积累不足且缓慢,以及随后的 T 细胞增殖,仍然是 F MRI 体内细胞成像的局限性。

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