Olsson T, Bakhiet M, Edlund C, Höjeberg B, Van der Meide P H, Kristensson K
Department of Neurology, Karolinska Institutet, Huddinge University Hospital, Sweden.
Eur J Immunol. 1991 Oct;21(10):2447-54. doi: 10.1002/eji.1830211022.
The hemoflagellate Trypanosoma brucei (T.b.) is the cause of African sleeping sickness. T. b. brucei which is pathogenic for rodents but nonpathogenic for humans was used to examine the interactions between the parasite and mononuclear cells (MNC). Co-cultivation in vitro of rat or human MNC and T.b. brucei resulted in a rapid non-antigen-specific release of interferon-gamma (IFN-gamma) which was dependent on CD8+ lymphoid cells. The parasites triggered MNC proliferation if IFN-gamma was blocked by a specific antibody in vitro. Separate cultures of parasites and MNC in a two-chamber system allowing exchange of soluble mediators showed CD8+ cell-dependent MNC triggering, indicating that a diffusable factor released by trypanosomes acts on the MNC. Gel filtration according to molecular mass of disrupted parasites and assay of the fractions revealed a peak activity at an approximate molecular mass of 185 kDa for the trypanosome-derived lymphocyte-triggering factor (TLTF). Conversely, there was a CD8+ cell-dependent action of MNC on the trypanosomes. MNC released a diffusable factor that in short-term experiments caused a striking increase in number of parasites. This effect was inhibited by antibodies against rat IFN-gamma. The increase in number of trypanosomes was promoted by rat MNC or rat IFN-gamma but not human MNC or human IFN-gamma suggesting a species-restricted recognition of IFN-gamma. An in vivo uptake of IFN-gamma by the parasites was suggested by immunohistochemical staining of T.b. brucei with an mAb against rat IFN-gamma and Western blot of the parasites showing a band with a molecular mass corresponding to IFN-gamma. The bidirectional signals we define here may explain certain features of trypanosomiasis, i.e. T cell activation, immunosuppression and host-range restriction. The seemingly important role of the TLTF indicates that it should be purified and explored as target for immune-specific intervention.
血液鞭毛虫布氏锥虫（T.b.）是非洲昏睡病的病原体。对啮齿动物致病但对人类无致病性的布氏布氏锥虫（T. b. brucei）被用于研究寄生虫与单核细胞（MNC）之间的相互作用。大鼠或人类MNC与T.b. brucei的体外共培养导致干扰素-γ（IFN-γ）迅速非抗原特异性释放，这依赖于CD8 +淋巴细胞。如果在体外IFN-γ被特异性抗体阻断，寄生虫会触发MNC增殖。在允许可溶性介质交换的双室系统中分别培养寄生虫和MNC，显示出CD8 +细胞依赖性的MNC触发，表明锥虫释放的一种可扩散因子作用于MNC。根据破碎寄生虫的分子量进行凝胶过滤并分析各组分，发现锥虫来源的淋巴细胞触发因子（TLTF）在大约185 kDa的分子量处有一个活性峰。相反，MNC对锥虫有CD8 +细胞依赖性作用。MNC释放一种可扩散因子，在短期实验中导致寄生虫数量显著增加。这种效应被抗大鼠IFN-γ抗体抑制。锥虫数量的增加由大鼠MNC或大鼠IFN-γ促进，但不由人类MNC或人类IFN-γ促进，这表明对IFN-γ存在物种限制的识别。用抗大鼠IFN-γ的单克隆抗体对T.b. brucei进行免疫组织化学染色以及对寄生虫进行蛋白质印迹分析，显示出一条分子量对应于IFN-γ的条带，提示寄生虫在体内摄取了IFN-γ。我们在此定义的双向信号可能解释了锥虫病的某些特征，即T细胞活化、免疫抑制和宿主范围限制。TLTF看似重要的作用表明应将其纯化并作为免疫特异性干预的靶点进行探索。
