Raqib R, Ljungdahl A, Lindberg A A, Andersson U, Andersson J
International Centre for Diarrhoeal Diseases Research, Dhaka, Bangladesh.
Gut. 1996 Mar;38(3):328-36. doi: 10.1136/gut.38.3.328.
In healthy controls (n = 8) living in shigella endemic areas, accumulation of interferon gamma (IFN gamma) in the epithelial lining was seen in the rectal tissues. At the single cell level, however, few or no IFN gamma protein producing cells or mRNA expressing cells were detected at that site indicating the involvement of the whole large intestine in the production of IFN gamma in controls. Persistent numbers of IFN gamma producing cells were detected in the rectum of patients with Shigella dysenteriae type 1 infection (n = 8) throughout the course of disease with a tendency to increase in the convalescent stage. A significantly increased extra cellular deposition of secreted IFN gamma in tissue was seen in convalescence when compared with the acute stage (p < 0.05). In addition, enzyme immunoassay showed increased stool concentration of IFN gamma in patients at the convalescent stage as well as in healthy controls. In situ hybridisation confirmed the results by showing increased frequency of IFN gamma mRNA containing cells at the late stage of the disease (p < 0.05). Extensive message for IFN gamma was evident in cells in the lamina propria with no detectable transcripts in the surface epithelium. A colocalisation of IFN gamma with the IFN gamma receptor expression, predominantly found in the epithelial lining was detected by immunohistochemistry. Semiquantitative evaluation by computerised image analysis showed a gradual increased expression of IFN gamma and its corresponding receptor in the convalescent stage of shigellosis. This suggested progressive entrapment and binding of IFN gamma to its specific receptor at the local site. The enhanced surface expression of IFN gamma receptor evident at the convalescent stage of shigellosis was comparable to the constitutive level of expression in the healthy subjects. Thus, immunity to shigellosis correlated to up-regulation of IFN gamma production and expression of IFN gamma receptor.
在生活在志贺氏菌流行地区的健康对照者(n = 8)中,在直肠组织的上皮衬里中可见干扰素γ(IFNγ)的积累。然而,在单细胞水平上,在该部位几乎未检测到或未检测到产生IFNγ蛋白的细胞或表达mRNA的细胞,这表明在对照者中整个大肠参与了IFNγ的产生。在1型痢疾志贺氏菌感染患者(n = 8)的整个病程中,在直肠中检测到持续数量的产生IFNγ的细胞,在恢复期有增加的趋势。与急性期相比,恢复期组织中分泌的IFNγ的细胞外沉积明显增加(p < 0.05)。此外,酶免疫测定显示,恢复期患者以及健康对照者粪便中IFNγ的浓度增加。原位杂交通过显示疾病后期含有IFNγ mRNA的细胞频率增加来证实了这一结果(p < 0.05)。在固有层细胞中IFNγ的广泛信息很明显,而表面上皮中未检测到转录本。通过免疫组织化学检测到IFNγ与IFNγ受体表达的共定位,主要存在于上皮衬里中。通过计算机图像分析进行的半定量评估显示,在志贺氏菌病恢复期,IFNγ及其相应受体的表达逐渐增加。这表明IFNγ在局部部位逐渐被捕获并与其特异性受体结合。在志贺氏菌病恢复期明显增强的IFNγ受体表面表达与健康受试者的组成性表达水平相当。因此,对志贺氏菌病的免疫与IFNγ产生的上调和IFNγ受体的表达相关。