The Center of Research & Development, Ruichuang Biotechnology Company, Shaoxing City, Zhejiang Province, China.
The Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CDSER/SIMM), Shanghai City, China.
Biopharm Drug Dispos. 2021 Jul;42(7):338-347. doi: 10.1002/bdd.2295. Epub 2021 Jul 3.
This study was intended to delineate the profile of double-negative T cells (DNTs) in NOD.Cg-Prkdc Il2rg /SzJ mice and cytokines released from DNTs in vivo and in vitro. Total 4 × 10 cells of RC1012 injection per mice were intravenously infused. IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10 were measured in vivo and in vitro. A quantitative polymerase chain reaction (PCR) was employed to determine the gene copies of Notch2-NLA per DNT cell from collected organs. Cytokines were significantly increased in vitro (4 h) and in vivo (3 h). DNT cells were distributed into the lung, liver, heart, and kidney earlier, and redistributed to lymphocyte homing spleen and bone marrow, which seemed to frame a two-compartment pharmacokinetics (PK) model but more data are needed to confirm this, and the clearance of DNT cells fell into first-order kinetics.
本研究旨在描绘 NOD.Cg-Prkdc Il2rg /SzJ 小鼠中双阴性 T 细胞（DNT）的特征，以及 DNT 在体内和体外释放的细胞因子。每只小鼠静脉注射 4×10 个 RC1012 细胞。在体内和体外测量 IFN-γ、TNF-α、IL-1β、IL-2、IL-4、IL-6、IL-10。采用定量聚合酶链反应（PCR）测定从采集器官的每个 DNT 细胞中 Notch2-NLA 的基因拷贝数。细胞因子在体外（4 小时）和体内（3 小时）均显著增加。DNT 细胞较早分布在肺、肝、心和肾中，然后重新分布到淋巴细胞归巢的脾脏和骨髓中，这似乎构成了双室药代动力学（PK）模型，但需要更多数据来证实这一点，DNT 细胞的清除呈一级动力学。
