Identification of cytosine-phosphorothioate-guanine oligodeoxynucleotide sequences that induce interferon-γ production in feline immune cells
Identification of cytosine-phosphorothioate-guanine oligodeoxynucleotide sequences that induce interferon-γ production in feline immune cells
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DOI：
10.1111/j.1348-0421.2010.00298.x
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发表时间：
2011-03-01
影响因子：
2.6
通讯作者：
Hohdatsu, Tsutomu
中科院分区：
文献类型：
--
作者：
Satoh, Ryoichi;Kotake, Masako;Hohdatsu, Tsutomu
已知未甲基化的CpG-ODN可增强Th1型免疫反应。然而，激活Th1型免疫细胞的CpG-ODN的最佳序列因物种而异。有必要鉴定每个物种中的有效CpG-ODN序列。为了确定在猫体内产生干扰素-γ的CpG-ODN序列，我们合成了14种寡核苷酸，并检测了它们在猫的PBMC和脾细胞中诱导干扰素-γ的能力。结果表明，部分CpG-ODN可显著诱导脾细胞产生干扰素-γ，但对PBMC无明显影响。我们发现3种CpG-ODN(2，5‘-ggTGCATCGATGCAGggG-3’；5，5‘-ggTGCGTCGACGCAGggG-3’；10，5‘-ggTGCTACGTAGCAGggG-3’)能显著诱导猫脾细胞产生γ-干扰素。反向序列GPC-ODN不会引起显著的干扰素-γ产生。CpG-ODN nos混合物产生干扰素-γ的诱生能力。2、5和10个CpG-ODN均高于单个CpG-ODN。将CpG-ODN混合物包裹在MCL中，给猫注射后，PBMC中的干扰素-γ+细胞数显著增加。CpG-ODN nos.作为疫苗佐剂，2、5和10应可用于诱导猫的Th1型免疫反应。
Unmethylated CpG-ODN are known to enhance Th1-type immune response. However, optimal sequences of CpG-ODN for activating Th1-type immune cells vary among species. It is necessary to identify the effective CpG-ODN sequences in each species. In the present study, in order to identify the sequences of CpG-ODN that produce fIFN-gamma in cats, 14 kinds of ODN were synthesized and examined regarding their ability to induce fIFN-gamma in feline PBMC and splenocytes. It was shown that some CpG-ODN significantly induced fIFN-gamma production in splenocytes, but not in PBMC. We found that three kinds of CpG-ODN (no. 2, 5 '-ggTGCATCGATGCAGggggG-3 '; no. 5, 5 '-ggTGCGTCGACGCAGggggG-3 '; no. 10, 5 '-ggTGCTACGTAGCAGggggG-3 ') specifically and significantly induced fIFN-gamma production in feline splenocytes. The reverse sequences, GpC-ODN, do not cause significant fIFN-gamma production. The fIFN-gamma production inductivity of a mixture of CpG-ODN nos. 2, 5 and 10 was higher than those of individual CpG-ODN. When the CpG-ODN mixture was encapsulated in an MCL and administrated to cats, the number of fIFN-gamma+ cells in PBMC significantly increased. CpG-ODN nos. 2, 5 and 10 should be useful to elicit a Th1-type immune response as a vaccine adjuvant in cats.