PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner
PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner
复制标题
DOI：
10.1016/j.jconrel.2007.05.015
复制
发表时间：
2007-10-08
影响因子：
10.8
通讯作者：
Kiwada, Hiroshi
中科院分区：
文献类型：
--
作者：
Ishida, Tatsuhiro;Wang, Xinyu;Kiwada, Hiroshi
我们最近报道，静脉注射的“空”PEG化脂质体没有封装或表面偶联蛋白引起的PEG特异性IgM反应在大鼠。在本研究中，在静脉注射“空”PEG化脂质体后，同时检测到弱抗PEG IgG和强抗PEG IgM应答。免疫应答的模式似乎不同于针对T细胞依赖性（TD）抗原的经典初级应答。在静脉内注射“空的”PEG化脂质体后，在T细胞缺陷的裸BALB/c小鼠中检测到抗PEG IgM应答，表明“空的”PEG化脂质体以T细胞非依赖性方式启动针对PEG的免疫应答。体外脾淋巴细胞增殖试验表明，TNP-LPS，一种典型的1型T细胞非依赖性（TI）抗原（TI-1抗原），显着引发增殖，而TNP-Ficoll，一种典型的2型TI抗原（TI-2抗原），和“空”聚乙二醇化脂质体没有引发任何增殖在这些实验条件下。此外，在脾边缘区（MZ）B细胞耗竭大鼠中，抗PEG IgM反应减弱，而对TNP-BSA（TD抗原）和TNP-LPS（TI-1抗原）的免疫反应并未减弱。这些结果表明，“空”PEG化脂质体可促进针对PEG的免疫应答，这是由于引发MZ B细胞的活化，因为TI-2抗原促进特异性IgM应答。总之，尽管针对“空”聚乙二醇化脂质体的免疫反应背后的机制细节尚不清楚，但脂质体以T细胞非依赖性方式引发抗PEG IgM应答，并且似乎是TI-2抗原，并且脾MZ B细胞对于针对“空”聚乙二醇化脂质体的免疫应答可能是必需的。(C)2007 Elsevier B. V.保留所有权利。
We recently reported that intravenous injections of "empty" PEGylated liposomes without encapsulated or surface coupled proteins elicit a PEG-specific IgM response in rats. In the present study, simultaneous weak anti-PEG IgG and strong anti-PEG IgM responses were detected following intravenous injections of "empty" PEGylated liposomes. The pattern of immune response appears to differ from the classic primary response against T cell-dependent (TD) antigens. The anti-PEG IgM response was detected in T-cell deficient nude BALB/c mice following intravenous injection of "empty" PEGylated liposomes, suggesting that "empty" PEGylated liposomes initiate the immune response against PEG in a T cell-independent manner. In vitro splenic lymphocytes-proliferation assay indicated that TNP-LPS, a typical type 1 T cell-independent (TI) antigen (TI-1 antigen), significantly primed the proliferation, while TNP-Ficoll, a typical type 2 TI antigen (TI-2 antigen), and "empty" PEGylated liposomes did not prime any proliferation under these experimental conditions. In addition, in splenic marginal zone (MZ) B-cell-depleted rats, the anti-PEG IgM response was diminished, while the immune reactions against TNP-BSA (a TD antigen) and TNP-LPS (TI-1 antigen) were not diminished. These results demonstrate that "empty" PEGytated liposomes may promote the immune response against PEG as a result of priming the activation of MZ B cells, as TI-2 antigen promotes a specific IgM response. In conclusion, although the mechanistic details behind the immune reaction against "empty" PEGylated liposomes are not yet clear, the liposomes elicit an anti-PEG IgM response in a T cell-independent manner and appear to be a TI-2 antigen, and splenic MZ B cells may be essential for the immune response against "empty" PEGylated liposomes. (C) 2007 Elsevier B.V. All rights reserved.