Analysis of the role of vaccine adjuvants in modulating dendritic cell activation and antigen presentation in vitro

Analysis of the role of vaccine adjuvants in modulating dendritic cell activation and antigen presentation in vitro
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DOI:
10.1016/s0264-410x(02)00531-5
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发表时间:
2003-02-14
期刊:
影响因子:
5.5
通讯作者:
Brewer, JM
Brewer, JM
中科院分区:
医学3区
文献类型:
--
作者:
Sun, HF;Pollock, KGJ;Brewer, JM

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我们研究了佐剂制剂对骨髓来源的树突状细胞(DC)的活化和抗原呈递功能的影响。虽然LPS可以诱导DC上高水平表达MHC II类分子和共刺激分子,但它并没有增强抗原提呈至共刺激非依赖性DO 11。GFPT杂交瘤细胞。相比之下,明矾、NISV和PLGA制剂不能激活DC,但NISV和PLGA可以将抗原呈递效率提高10-100倍。不管先前描述的每种佐剂的抗原释放特性如何,对于所有制剂,抗原呈递在6 μ l时达到峰值,此后减弱。考虑到DC在初始T细胞应答的活化中的重要性,这些研究表明,体内DC活化的尚未确定的途径可能是明矾、PLGA和NISV佐剂活性的基础。此外,由于NISV和PLGA在DC中似乎不起缓释系统的作用,这些颗粒系统诱导DC高水平抗原呈递的能力可能在其佐剂活性中具有更重要的作用。(C)2002爱思唯尔科技有限公司版权所有。
We have studied the effects of adjuvant formulations on the activation and antigen-presenting functions of bone marrow-derived dendritic cells (DCs). While LPS could induce high-level expression of MHC Class II and co-stimulator molecules on DCs, it did not enhance antigen presentation to co-stimulation independent DO11. GFPT hybridoma cells. In contrast, alum, NISV and PLGA formulations failed to activate DCs, but NISV and PLGA could enhance antigen-presentation efficiency by 10-100-fold. Irrespective of the previously described antigen release characteristics of each adjuvant, antigen presentation peaked at 6 It and waned thereafter for all formulations. Given the importance of DCs in the activation of naive T cell responses, these studies suggest that as yet undefined pathways of DC activation in vivo may underlie the activity of alum, PLGA and NISV adjuvants. Furthermore, as NISV and PLGA do not appear to act as slow-release systems in DCs, the ability of these particulate systems to induce high levels of antigen presentation by DCs probably has a more significant role in their adjuvant activity. (C) 2002 Elsevier Science Ltd. All rights reserved.