IFN-αβ promote priming of antigen-specific CD8+ and CD4+ T lymphocytes by immunostimulatory DNA-based vaccines
IFN-αβ promote priming of antigen-specific CD8+ and CD4+ T lymphocytes by immunostimulatory DNA-based vaccines
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DOI：
10.4049/jimmunol.168.10.4907
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发表时间：
2002-05-15
影响因子：
4.4
通讯作者：
Raz, E
中科院分区：
文献类型：
--
作者：
Cho, HJ;Hayashi, T;Raz, E
含有未甲基化 CpG 二核苷酸的免疫刺激序列 (ISS) DNA 刺激 NK 和 APC 分泌促炎细胞因子，包括 IFN-alphabeta 和 -gamma、TNF-alpha、IL-6 和 -12，并表达共刺激表面分子，例如 CD40、B7-1 和 137-2。尽管按照这些标准，ISS DNA 对 T 细胞几乎没有直接影响，但用 ISS DNA 和 OVA 免疫野生型小鼠会产生 Ag 特异性 CTL 和 Th1 型 T 辅助活性。本研究探讨了 ISS DNA 启动 CD8(+) 和 CD4(+) 淋巴细胞活性的机制。在本报告中，我们证明 ISS DNA 通过新型自分泌或旁分泌 IFN-alphabeta 途径调节共刺激分子和 TAP 的表达。 B7共刺激和TAP依赖性交叉呈递的协调调节导致Ag特异性CD8(+) CTL的启动，而基于ISS的疫苗启动CD4(+) Th细胞需要CD40、137和IL-12共刺激。
Immunostimulatory sequence (ISS) DNA containing unmethylated CpG dinucleotides stimulate NK and APC to secrete proinflammatory cytokines, including IFN-alphabeta and -gamma, TNF-alpha, and IL-6 and -12, and to express costimulatory surface molecules such as CD40, B7-1, and 137-2. Although ISS DNA has little direct effect on T cells by these criteria, immunization of wild-type mice with ISS DNA and OVA results in Ag-specific CTL and Th1-type T helper activity. This investigation examines the mechanisms by which ISS DNA primes CD8(+) and CD4(+) lymphocyte activities. In this report we demonstrate that ISS DNA regulates the expression of costimulatory molecules and TAP via a novel autocrine or paracrine IFN-alphabeta pathway. Coordinated regulation of B7 costimulation and TAP-dependent cross-presentation results in priming of Ag-specific CD8(+) CTL, whereas CD40, 137, and IL-12 costimulation is required for priming of CD4(+) Th cells by ISS-based vaccines.