Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles
Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles
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DOI：
10.1016/s0022-1759(01)00433-1
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发表时间：
2001-10-01
影响因子：
2.2
通讯作者：
Mountz, JD
中科院分区：
文献类型：
--
作者：
Dodd, CH;Hsu, HC;Mountz, JD
本研究分析了用超顺磁性氧化铁（CLIO）纳米颗粒（由HIV-1反激活蛋白（Tat）的肽序列衍生而成）加载T细胞后，利用磁共振成像（MRI）监测T细胞在体内归一的可行性。从C57BL/6 （B6）小鼠中分离T细胞，分别加载0、400、800、1600或8000 ng/ml的FITC共轭CLIO-Tat （FITC-CLIO-Tat）。T细胞对FITC-CLIO-Tat的摄取呈剂量依赖性。用抗cd3 （0.1 mug/ml）和IL-2 （5 ng/ml）刺激装载FITC-CLIO-Tat的T细胞，可引起正常活化和活化诱导的细胞死亡（AICD）反应，以及CD69、ICAM-1 （CD54）、l -选择素（CD62L）和Fas的正常上调。将装载FITC-CLIO-Tat的T细胞（3 X 10(7)）静脉（i.v）转移到B6小鼠体内，并使用Bruker Biospec系统在4.7 T下使用自旋回波脉冲序列获得小鼠的体内MRI。移植后，MRI信号强度降低，并持续2-24小时，观察到T细胞归巢到脾脏。这些归巢数据经FACS分析和I-125-CLIO-Tat生物分布分析证实。因此，T细胞可以有效地装载FITC-CLIO-Tat，而不会干扰其正常激活和AICD，也不会归巢到脾脏，并且FITC-CLIO-Tat装载的T细胞可以通过MRI在体内监测其生物分布。(C) 2001 Elsevier Science B.V.版权所有
The present study analyzed the feasibility of using magnetic resonance imaging (MRI) to monitor T-cell homing in vivo after loading T cells with superparamagnetic iron oxide (CLIO) nanoparticles derivatized with a peptide sequence from the transactivator protein (Tat) of HIV-1. T cells were isolated from C57BL/6 (B6) mice and loaded with 0, 400, 800, 1600, or 8000 ng/ml of FITC conjugated CLIO-Tat (FITC-CLIO-Tat). There was a dose-dependent uptake of FITC-CLIO-Tat by T cells. Stimulation of FITC-CLIO-Tat loaded T cells with anti-CD3 (0.1 mug/ml) plus IL-2 (5 ng/ml) elicited normal activation and activation-induced cell death (AICD) responses, and normal upregulation of CD69, ICAM-1 (CD54), L-selectin (CD62L), and Fas. The FITC-CLIO-Tat loaded T cells (3 X 10(7)) were transferred intravenously (i.v.) into B6 mice and the in vivo MRI of mice was acquired using a spin-echo pulse sequence at 4.7 T with a Bruker Biospec system. Homing of T cells into the spleen was observed by a decrease in MRI signal intensity within I It after the transfer, which remained decreased for 2-24 h after transfer. These homing data were confirmed by FACS analysis and biodistribution analysis using I-125-CLIO-Tat. Thus, T cells can be efficiently loaded with FITC-CLIO-Tat without interfering with their normal activation and AICD, or homing to the spleen, and the biodistribution of FITC-CLIO-Tat loaded T cells can be monitored in vivo over time by MRI. (C) 2001 Elsevier Science B.V. All rights reserved.