A study on involvement of cytokines in immune response to parasite infections using immune response-reacted gene defective mice

细胞因子在宿主对寄生虫的反应中发挥着多种重要的调节作用。为了分析寄生虫感染的复杂免疫反应，我们利用干扰素-γ受体和IL-4基因敲除小鼠(分别为干扰素-γ受体和IL-4基因敲除小鼠)、对主要致病菌有抵抗力的野生型C57BL/6小鼠和对该菌有抵抗力的野生型BALB/c MICC小鼠，研究了干扰素-γ和IL-4对寄生虫感染的影响。得到的结果如下。1.IL-4^%和C57BL/6小鼠皮下感染大鼠后，均出现轻度足肿胀。另一方面，干扰素-γR^%和BALB/c小鼠感染大鼠的足垫肿胀程度较高。2.用酶联免疫斑点法和流式细胞术检测BALB/c和C57BL/6小鼠脾、脾和肝组织中产生干扰素-γ和IL-4的细胞数量。反应如下。(1)在主要抗原存在下，BALB/c和C57BL/6小鼠均可检测到干扰素-γ产生细胞，且C57BL/6小鼠的干扰素-γ产生细胞数多于BALB/c小鼠。(2)感染后5周，两组小鼠的去抗原组织中均未检测到干扰素-γ产生细胞。(3)BALB/c小鼠的脾、肝组织中均可检测到IL-4产生细胞，且随感染时间的延长而增加。(4)BALB/c小鼠肝脏中产生IL-4的细胞表型为Gammadelta^+T细胞、Alphabeta^+T细胞和CD4^-CD8^-细胞。感染后2周Gammadelta^+T细胞增多，4周Alphabeta^+T细胞增多。CD4^-CD8^-细胞仅在感染早期产生IL-4。分析这些现象的研究目前正在进行中。

Cytokines play a variety of crucial regulatory roles in the host response to parasites. To analyze complecated immune responses in parasite infections, we investigated effects of IFN-gamma and IL-4 on parasite infections by using IFN-gamma receptor and IL-4 gene knockout mice (IFN-gamma R^% and IL-4^%, respectively), wild type C57BL/6 mice, resistant to L.major, and wild type BALB/c micc, suceptible to this organism. The obtained results are as follows. 1.IL-4^% and C57BL/6 mice showed a weak footpad swelling, when these mice were infected s.c.with L.major. On the other hand, high intensity of footpad swelling was observed in IFN-gamma R^% and BALB/c mice infected with L.major. 2.The number of IFN-gamma or IL-4 producing cells were measured in the popliteal lymphnodes, the spleen, and the liver of BALB/c and C57BL/6 mice using enzyme-linked immunospot assay and flow cytometry. The reaction as follows. (1) IFN-gamma Producing cells were detected in the presence of L.major antigens in BALB/c and C57BL/6 mice, and the number of the IFN-gamma Producing cells in C57BL/6 mice was more than that in BALB/c mice. (2) The IFN-gamma producing cells could not be detected in vitro in the abscence of the antigens in both mice by 5 weeks post infection. (3) IL-4 producing cells were detected from the spleen and the liver of BALB/c mice and increased with the progress of the infection. (4) Phenotype of IL-4 producing cells in the liver of BALB/c mice were gammadelta^+T cells, alphabeta^+T cells, and CD4^-CD8^- cells. gammadelta^+T cells incrcased at 2 week post infection and alphabeta^+T cells incrcased at 4 week. CD4^-CD8^- cells produced IL-4 during only early phase of the infection. Studies to analyze these phenomena are currently underway.