Induction of the trypanosome lymphocyte-triggering factor (TLTF) and neutralizing antibodies to the TLTF in experimental African trypanosomiasis
Induction of the trypanosome lymphocyte-triggering factor (TLTF) and neutralizing antibodies to the TLTF in experimental African trypanosomiasis
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DOI：
10.1046/j.1365-2567.1999.00730.x
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发表时间：
1999-04-01
期刊：
影响因子：
6.4
通讯作者：
Bakhiet, M
中科院分区：
文献类型：
--
作者：
Hamadien, M;Lycke, N;Bakhiet, M
我们已经证明非洲锥虫会分泌一种新型锥虫因子，即锥虫衍生的淋巴细胞触发因子（TLTF），它可以激活CD8+细胞产生干扰素-γ（IFN-γ），进而刺激寄生虫生长。 TLTF 基因最近被克隆，重组 TLTF (rTLTF) 显示出与天然 TLTF 相似的生物活性。在这项工作中，我们使用两种抗 TLTF 单克隆抗体 (mAb) 来检测小鼠布氏锥虫 (T. b. billcei) 感染期间的 TLTF 水平。此外，rTLTF 用于评估抗 TLTF 抗体的水平。对具有完整基因的小鼠（野生型）和具有破坏的 IFN-γ (IFN-γ(- / -)) 或 IFN-γ R (IFN-γ R- / -) 基因的敲除小鼠进行了研究。使用基因敲除小鼠来说明 IFN-γ 在 TLTF 抗体产生中的作用。而野生型小鼠在感染后第 3 天（p.i.）表现出高寄生虫血症，并伴有高 TLTF 水平和低抗 TLTF 抗体。在注射后第 21 天测量到低 TLTF 和增加的抗 TLTF 抗体。 IFN-γ(- / -)小鼠表现出非常低的寄生虫血症、TLTF和抗TLTF抗体水平。相反，IFN-γ R-/-小鼠表现出非常高的寄生虫血症，TLTF水平升高，但抗TLTF抗体降低。在 TLTF 的生物测定中，抗 TLTF 抗体的 Fab' 片段剂量依赖性地抑制脾细胞 TLTF 诱导的 IFN-γ 产生，表明这些抗体的调节重要性。我们的数据证明了 IFN-γ 在 TLTF 中和抗体生成中的作用。此外，TLTF及其抗体的诱导可能构成未来诊断非洲锥虫病的新方法。
We have demonstrated that African trypanosomes secrete a novel trypanokine, the trypanosome-derived lymphocyte-triggering factor (TLTF), which activates CD8(+) cells to produce iinterferon-gamma (IFN-gamma) that in turn stimulates parasite growth. The gene for TLTF was recently cloned, and recombinant TLTF (rTLTF) showed bioactivity that was similar to native TLTF. In this work, we employed two anti-TLTF monoclonal antibodies (mAbs) to detect levels of TLTF during Trypanosoma brucei brucei (T. b. billcei) infections in mice. Furthermore, rTLTF was utilized to assess levels of anti-TLTF antibodies. Mice with intact genes (wild type), and knockout mice with disrupted IFN-gamma (IFN-gamma(- / -)) or IFN-gamma R (IFN-gamma R- / -) genes were studied. The knockout mice were used in order to illustrate the role of IFN-gamma in the production of antibodies to TLTF. While wild-type mice showed high parasitaemia accompanied by high TLTF levels and low anti-TLTF antibodies at day 3 postinfection (p.i.). low TLTF was measured together with increased anti-TLTF antibodies at day 21 p.i. IFN-y(- / -) mice exhibited very low parasitaemia, TLTF and anti-TLTF antibody levels. In contrast, IFN-gamma R- / - mice revealed very high parasitaemia, increased TLTF levels, but decreased anti-TLTF antibodies. In a biological assay for TLTF, Fab' fragments of anti-TLTF antibodies dose dependently inhibited the TLTF-induced IFN-gamma production by splenocytes, suggesting a regulatory importance of these antibodies. Our data demonstrate a role of IFN-gamma in the generation of neutralizing antibodies to TLTF. Furthermore, the induction of TLTF and its antibodies may constitute a new approach for future diagnosis of African trypanosomiasis.