Stimulation of in vitro murine lymphocyte proliferation by bacterial DNA.
Stimulation of in vitro murine lymphocyte proliferation by bacterial DNA.
复制标题
DOI：
10.4049/jimmunol.147.6.1759
复制
发表时间：
1991-09
影响因子：
4.4
通讯作者：
J. Messina;G. Gilkeson;D. Pisetsky
中科院分区：
文献类型：
--
作者：
J. Messina;G. Gilkeson;D. Pisetsky
尽管 DNA 通常被认为是一种较差的免疫原，但最近的证据表明，不同物种的 DNA 的免疫活性不同，并且细菌 DNA 与哺乳动物 DNA 不同，可以在小鼠体内诱导显着的抗体反应。为了进一步探索细菌DNA的免疫活性，测试了其刺激小鼠淋巴细胞体外增殖的能力。用来自大肠杆菌的高度纯化的 ssDNA 刺激淋巴细胞会产生剂量依赖性反应，该反应在 48 小时时达到最大。多项证据表明，引起这种反应的是 DNA，而不是内毒素污染：1) 与 DNA 制剂中检测到的剂量相当的 LPS 引起的增殖明显低于 DNA； 2) 对DNA的反应对多粘菌素B不敏感； 3) 用 DNase 预处理 DNA 完全消除了反应； 4) DNA诱导内毒素抗性C3H/HeJ小鼠细胞增殖。此外，虽然来自三种不同细菌物种的 DNA 诱导增殖，但来自三个物种的哺乳动物 DNA 是非有丝分裂的。淋巴细胞中 T 细胞的消耗并没有减少增殖，这表明细菌 DNA 直接触发了 B 细胞增殖。这些研究提供了进一步的证据，表明 DNA 的免疫活性不一致，可能是因为它们含有非保守结构决定簇。
Although DNA is generally considered to be a poor immunogen, recent evidence suggests that DNA from various species differ in their immunologic activity and that bacterial DNA, unlike mammalian DNA, can induce significant antibody responses in mice. To explore further the immunologic activities of bacterial DNA, its ability to stimulate in vitro proliferation of murine lymphocytes was tested. The stimulation of lymphocytes with highly purified ssDNA from Escherichia coli resulted in a dose-dependent response that was maximal at 48 h. Several lines of evidence indicate that DNA, rather than endotoxin contamination, induced this response: 1) LPS at doses equivalent to those detected in the DNA preparation caused significantly less proliferation than the DNA; 2) the response to DNA was insensitive to polymyxin B; 3) pretreatment of DNA with DNase completely abrogated the response; and 4) DNA induced the proliferation of cells from endotoxin-resistant C3H/HeJ mice. Furthermore, although DNA from three different bacterial species induced proliferation, mammalian DNA from three species were nonmitogenic. Depletion of T cells from lymphocytes did not reduce proliferation, suggesting that bacterial DNA directly triggered B cell proliferation. These studies provide further evidence that DNA are not uniform in their immunologic activities likely because of their content of nonconserved structural determinants.