The timing of GM-CSF expression plasmid administration influences the Th1/Th2 response induced by an HIV-1-specific DNA vaccine
The timing of GM-CSF expression plasmid administration influences the Th1/Th2 response induced by an HIV-1-specific DNA vaccine
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DOI：
10.4049/jimmunol.164.6.3102
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发表时间：
2000-03-15
影响因子：
4.4
通讯作者：
Okuda, K
中科院分区：
文献类型：
--
作者：
Kusakabe, K;Xin, KQ;Okuda, K
研究了编码粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）的质粒（pGM - CSF）与编码人类免疫缺陷病毒（HIV）包膜的DNA疫苗联合使用所诱导的免疫激活机制。在DNA疫苗接种前3天对小鼠肌肉注射pGM - CSF主要诱导了Th2反应。同时给予DNA疫苗和pGM - CSF可激活Th1和Th2反应。当在DNA疫苗接种3天后注射该质粒时，以Th1免疫增强为主。这些结果表明，细胞因子表达的时间决定了所产生的Th反应的表型。在注射pGM - CSF 3天后，在局部淋巴结中观察到CD11c（+）、CD8（+）细胞百分比增加。此外，在注射pGM - CSF的组织中发现了许多浸润细胞，包括S - 100蛋白阳性细胞。还研究了这些S - 100（+）细胞以及CD8（+）和CD11c（+）细胞（特别是树突状细胞（DCs））的重要性。从骨髓中获取并在含有白细胞介素 - 4（IL - 4）和GM - CSF的RPMI 1640培养基中培养的树突状细胞与DNA疫苗一起孵育，然后转移到未免疫的小鼠体内。接受树突状细胞的小鼠表现出强烈的HIV - 1特异性Th2免疫反应。我们的研究结果表明，树突状细胞在DNA疫苗接种诱导的Th2型免疫反应的激活或调节中起重要作用。
The mechanism of immune activation induced by a plasmid-encoding GM-CSF (pGM-CSF), administered in combination with a DNA vaccine encoding the envelope of HIV, was studied. Injecting pGM-CSF i.m. into mice 3 days before DNA vaccination primarily induced a Th2 response. Simultaneous administration of the DNA vaccine plus pGM-CSF activated both a Th1 and a Th2 response. When the plasmid was injected 3 days after DNA vaccination, enhancement of Th1 immunity predominated. These results suggest that the timing of cytokine expression determines the phenotype of the resultant Th response. After 3 days of pGM-CSF injection, the increased percentages of CD11c(+), CD8(+) cells were observed in the regional lymph nodes. In addition, many infiltrated cells, including S-100 protein-positive cells, were found in the pGM-CSF-injected tissue. The importance of these S-100(+) cells or both CD8(+) and CD11c(+) cells, especially that of dendritic cells (DCs), was also studied. DCs derived from bone marrow and cultured in RPMI 1640 medium containing IL-4 and GM-CSF were incubated with DNA vaccine and then transferred into naive mice. Mice receiving DCs showed strong HIV-1-specific Th2 immune responses. Our results suggest that DCs play important roles in the activation or modification of the Th2-type immune response induced by DNA vaccination.