Morrison W I, MacHugh N D, Lalor P A
Institute for Animal Health, Compton, United Kingdom.
Infect Immun. 1996 Feb;64(2):557-62. doi: 10.1128/iai.64.2.557-562.1996.
Theileria parva has been shown to infect and transform B cells and T cells at similar frequencies in vitro. However, the majority of parasitized cells in the tissues of infected cattle are alpha/beta T cells. The aim of this study was to determine whether the cell type infected with T. parva influenced the pathogenicity of the parasite. The initial approach, which involved inoculation of cattle with autologous cloned cell lines of different phenotypes, failed to resolve the issue, because of prolonged period of culture required to clone and characterize the cell lines resulted in attenuation of the cells. As an alternative approach, cattle were inoculated with purified populations of autologous cells that had been incubated in vitro with T. parva sporozoites for 48 h. As few as 3 x 10(4) peripheral blood mononuclear cells (PBMC) treated in this way were found to produce severe clinical reactions with high levels of parasitosis. Infections of similar severity were produced with purified populations of CD2+, CD4+, and CD8+ T cells. By contrast, infected B cells gave rise to mild self-limiting infections even when administered at a 10-fold-higher dose. In animals that received infected CD4+ or CD8+ T cells, the parasitized cells in the lymph nodes on day 11 of infection were all within the CD4+ and CD8+ populations, respectively, indicating that there had been minimal transfer of the parasite between cell types. Phenotypic analyses of cultures of PBMC infected in vitro with saturating concentrations of sporozoites revealed that parasitized B cells were abundant in the cultures after 1 week but were subsequently overgrown by T cells. The results of these experiments indicate that the cell type infected by T. parva influences the pathogenicity of the parasite.
已证明,在体外,小泰勒虫感染和转化B细胞及T细胞的频率相近。然而,感染牛组织中的大多数被寄生细胞是α/β T细胞。本研究的目的是确定感染小泰勒虫的细胞类型是否会影响该寄生虫的致病性。最初的方法是用不同表型的自体克隆细胞系接种牛,但未能解决该问题,因为克隆和鉴定细胞系所需的长时间培养导致细胞衰减。作为替代方法,给牛接种经体外与小泰勒虫子孢子孵育48小时的自体纯化细胞群体。发现以这种方式处理的低至3×10⁴外周血单个核细胞(PBMC)会产生严重的临床反应和高水平的寄生虫感染。用纯化的CD2⁺、CD4⁺和CD8⁺ T细胞群体也产生了类似严重程度的感染。相比之下,即使以高10倍的剂量给药,感染的B细胞也只会引发轻微的自限性感染。在接受感染的CD4⁺或CD8⁺ T细胞的动物中,感染第11天淋巴结中的被寄生细胞分别全部在CD4⁺和CD8⁺群体内,这表明细胞类型之间的寄生虫转移极少。用饱和浓度子孢子体外感染PBMC的培养物的表型分析显示,感染1周后培养物中被寄生的B细胞数量很多,但随后被T细胞过度生长。这些实验结果表明,感染小泰勒虫的细胞类型会影响该寄生虫的致病性。