Humphreys N E, Worthington J J, Little M C, Rice E J, Grencis R K
School of Biological Sciences, University of Manchester, UK.
Parasite Immunol. 2004 Apr;26(4):187-96. doi: 10.1111/j.0141-9838.2004.00702.x.
Chronic infection by the caecal-dwelling intestinal murine nematode Trichuris muris occurs if given as a high-dose infection to 'susceptible' AKR mice or as a low-dose infection to the normally 'resistant' C57BL/6 mouse strain. Both regimes result in a type 1 cytokine response, i.e. high levels of IFN-gamma and IL-12. Here we show this susceptible response is associated with a large population of CD8(+) IFN-gamma(+) cells within the mesenteric lymph nodes and numerous CD8(+) cells infiltrating the caecal mucosa. Despite this, the in vivo abolition of CD8(+) cells within AKR and C57BL/6 mice, either prior to infection or once infection has become established, failed to affect chronicity, implying that CD8(+) T cells are not essential for the initiation or maintenance of the susceptible response to T. muris. Interestingly, the percentage of IFN-gamma(+) CD4(+) cells increased in treated groups, perhaps in a compensatory role. The majority of antigen-specific cytokine responses were comparable in both treated and control groups, although IL-5 was fivefold higher in animals receiving anti-CD8 mAbs and IFN-gamma was also raised in treated mice. Mastocytosis was unaltered by CD8 depletion, however, paradoxically, eosinophilia within the caecum was reduced in treated mice. Together these data clearly demonstrate that CD8(+) T cells are associated with chronic T. muris infection; however, these cells are dispensable for both the early and late phases of this response, but do appear to play a role in the regulation of certain cytokines and caecal eosinophilia.
如果给“易感”的AKR小鼠高剂量感染或给通常“抗性”的C57BL/6小鼠品系低剂量感染,盲肠寄生的肠道鼠线虫毛首鞭形线虫就会引发慢性感染。这两种感染方式都会引发1型细胞因子反应,即高水平的干扰素-γ和白细胞介素-12。在此我们表明,这种易感反应与肠系膜淋巴结内大量的CD8(+)干扰素-γ(+)细胞以及众多浸润盲肠黏膜的CD8(+)细胞有关。尽管如此,在AKR和C57BL/6小鼠感染前或感染确立后体内清除CD8(+)细胞,并未影响感染的慢性化,这意味着CD8(+) T细胞对于对毛首鞭形线虫的易感反应的起始或维持并非必不可少。有趣的是,治疗组中干扰素-γ(+) CD4(+)细胞的百分比增加,可能起到了代偿作用。尽管接受抗CD8单克隆抗体的动物体内白细胞介素-5水平高出五倍,且治疗小鼠体内干扰素-γ水平也有所升高,但治疗组和对照组中大多数抗原特异性细胞因子反应相当。肥大细胞增多症并未因CD8细胞耗竭而改变,然而,矛盾的是,治疗小鼠盲肠内的嗜酸性粒细胞增多症有所减轻。这些数据清楚地表明,CD8(+) T细胞与毛首鞭形线虫慢性感染有关;然而,这些细胞在该反应的早期和晚期阶段都是可有可无的,但似乎在某些细胞因子的调节和盲肠嗜酸性粒细胞增多症中发挥作用。