Houston E Fiona, Taracha E L, Brackenbury Louise, MacHugh N D, McKeever D J, Charleston B, Morrison W I
Institute for Animal Health, Compton, Berkshire, RG20 7BH, UK.
Int J Parasitol. 2008 Dec;38(14):1693-704. doi: 10.1016/j.ijpara.2008.05.014. Epub 2008 Jun 12.
Theileria parva causes an acute lympho-proliferative disease in cattle, which can result in death of susceptible animals within 2-3 weeks of infection. Analyses of the cellular response in the lymph node draining the site of infection demonstrated an early T cell response, with the appearance of large numbers of uninfected lymphoblasts between 6 and 9 days p.i., coinciding with initial detection of parasitised cells. There was a marked increase in the representation of CD8(+) T cells and the emergence of a sizable sub-population of CD2(-) CD8(+) alpha/beta T cells during this period. Analysis of T cell receptor beta chain variable (TCR BV) gene expression did not reveal any evidence for the involvement of a superantigen in stimulating the response. Responding lymph node cells were found to produce increased quantities of IFNgamma and IL-10, and both the CD2(+) CD8(+) and CD2(-) CD8(+) populations expressed IFNgamma transcripts. Purified CD2(+) CD8(+) cells proliferated when stimulated in vitro with autologous parasitised cells or non-specific mitogens, whereas CD2(-) CD8(+) cells were refractory to these stimuli. In contrast to the parasite-specific cytotoxic activity associated with T cell responses in immune cattle, the responses to primary infection exhibited variable levels of non-specific cytotoxic activity. Stimulation of purified CD2(+) CD8(+) T cells in vitro with autologous parasitised cells also failed to reveal evidence of specific cytotoxic activity. These findings indicate that primary infection with T. parva induces an aberrant T cell response that lacks appropriate effector activity.
小泰勒虫可引发牛的急性淋巴细胞增殖性疾病,感染后2至3周内易感动物可能死亡。对感染部位引流淋巴结中的细胞反应分析表明,早期出现了T细胞反应,感染后6至9天出现大量未感染的淋巴母细胞,这与首次检测到被寄生细胞的时间一致。在此期间,CD8(+) T细胞的比例显著增加,同时出现了相当数量的CD2(-) CD8(+)α/β T细胞亚群。对T细胞受体β链可变区(TCR BV)基因表达的分析未发现有超抗原参与刺激该反应的证据。发现反应性淋巴结细胞产生的IFNγ和IL-10量增加,并且CD2(+) CD8(+)和CD2(-) CD8(+)群体均表达IFNγ转录本。纯化的CD2(+) CD8(+)细胞在体外被自体被寄生细胞或非特异性有丝分裂原刺激时会增殖,而CD2(-) CD8(+)细胞对这些刺激无反应。与免疫牛中与T细胞反应相关的寄生虫特异性细胞毒性活性不同,对初次感染反应表现出不同水平的非特异性细胞毒性活性。用自体被寄生细胞在体外刺激纯化的CD2(+) CD8(+) T细胞也未发现特异性细胞毒性活性的证据。这些发现表明,小泰勒虫的初次感染诱导了异常的T细胞反应,缺乏适当的效应活性。