衰老下调小鼠对日本血吸虫感染的免疫应答

Ageing Down-modulates the Immune Responses to Schistosoma japonicum Infection in Mice

目的研究衰老对小鼠感染日本血吸虫后免疫应答的影响。方法幼龄(2月龄)和老龄(18月龄)雌性BALB/c小鼠各8只,每鼠感染日本血吸虫尾蚴(40±1)条。感染后6周剖杀小鼠,经门静脉灌注收集成虫,计数虫荷;KOH消化法收集肝脏中的虫卵,并计数。制作肝脏连续病理切片,测量两组小鼠肝脏增生期平均单卵肉芽肿的大小,计算单卵肉芽肿体积。常规法制备脾淋巴细胞悬液进行T淋巴细胞增殖实验,计算刺激指数(SI)。ELISA法检测脾淋巴细胞中γ干扰素(IFN-γ)和白细胞介素4(IL-4)的表达水平。结果幼龄组小鼠体内的虫荷和每克肝组织虫卵数分别为26.00±2.42和(2.08±0.87)×104,老龄组虫荷和每克肝脏虫卵数分别为19.75±1.95和(1.59±1.05)×104,两组间的差异有统计学意义(P<0.05)。幼龄组肝脏单卵肉芽肿平均体积[(47.02±24.13)×10-3 mm3]明显大于老龄组[(30.13±10.97)×10-3 mm3](P<0.05)。T淋巴细胞增殖实验结果显示,老龄组脾淋巴细胞对ConA的增殖反应(SI:1.08±0.12)低于幼龄组(SI:1.31±0.14),其脾细胞培养上清中IFN-γ和IL-4的含量[(24.05±6.24)、(4.15±0.68)pg/ml]也明显低于幼龄组[(34.25±8.69)、(7.25±0.83)pg/ml](P<0.05)。结论衰老引起小鼠对日本血吸虫感染的免疫应答下降,从而减轻了日本血吸虫感染引起的免疫病理损害。

Objective To investigate the effect of ageing on the immune responses against Schistosoma japonicum infection in mice.Methods Female BALB/c mice were divided into young group（2 months） and old group（18 months）,each composed of 8 mice.Each mouse was percutaneously infected with 40±1 S.japonicum cercariae.At 6 weeks post-infection,the mice were sacrificed,and the spleens were removed and single-cell suspensions of splenocytes were prepared.Worms were perfused from hepatic portal system and counted.The number of eggs in the liver was determined after KOH digestion.Mean single-egg granulomas sizes were determined in stained histological sections.Splenocyte proliferation responses were analyzed by MTT colorimetry.Level of interferon-γ（IFN-γ） and interleukin-4（IL-4） in the splenocyte culture supernatants was deter-mined by ELISA.Results The worm burden and egg per gram of liver in old mice [19.75±1.95,（1.59±1.05）×104] were significantly lower than that of young mice [26.00±2.42,（2.08±0.87）×104]（P0.05）.The mean volume of single-egg granulomas of the livers in old mice [（30.13±10.97） ×10-3 mm3] was significantly lower than that of the young mice [（47.02±24.13） ×10-3 mm3]（P0.05）.Results of T cell proliferation showed that the splenocytes had poorer immune reactivity to ConA in old mice（SI： 1.08±0.12） than that in young mice（SI： 1.31±0.14）（P0.05）.Levels of IFN-γ and IL-4 in the splenocyte culture supernatants [（24.05±6.24）,（4.15±0.68） pg/ml] from old mice were lower than that of young mice [（34.25±8.69）,（7.25±0.83） pg/ml]（P0.05）.Conclusion Ageing down-modulates the immune responses and the poorer immune reactivity might decrease pathological alterations in mice infected with Schistosoma japonicum.