Storset A K, Hasvold H J, Valheim M, Brun-Hansen H, Berntsen G, Whist S K, Djønne B, Press C M, Holstad G, Larsen H J
Department of Pharmacology, Microbiology and Food Hygiene, The Norwegian School of Veterinary Science, P.O. Box 8146, N-0033 Oslo, Norway.
Vet Immunol Immunopathol. 2001 Aug 10;80(3-4):271-87. doi: 10.1016/s0165-2427(01)00294-x.
An experimental oral infection of goats with a caprine isolate of Mycobacterium a. subsp. paratuberculosis was used to investigate immunological and bacteriological events during the subclinical phase of infection. Seven goats at 5-8 weeks of age were given a bacterial suspension in milk-replacement three times weekly for 9 weeks. Six animals were kept as controls. Cellular recall responses against M. a. paratuberculosis were analysed by means of a lymphocyte proliferation test, an IFN-gamma assay and an IL-2 receptor assay. All inoculated animals had detectable CMI responses from 9 weeks post-inoculation and through the 2 years of study, although the responses were highest during the first year. Antibodies against M. a. paratuberculosis could be detected from weeks 15-20 in four of the seven animals, and one additional animal became antibody positive at week 35, while two inoculated animals did not produce significant antibody titres during the experiment. At about 1-year post-inoculation, two animals became faecal shedders, while two others started to excrete bacteria into faeces about 2 years post-inoculation. The appearance of M. a. paratuberculosis in faeces was not associated with a decline in cellular responses as far as could be assessed using the current methods for measuring CMI. Pathological lesions due to M. a. paratuberculosis infection and presence of bacteria were recorded in the intestine and/or mesenteric lymph nodes of five animals while lymph node changes suggestive of paratuberculosis were observed in one animal. Only the two animals with no signs of an active infection at necropsy showed a considerable decline in the cellular parameters during the last year of the study, particularly in the IFN-gamma assay. The two animals with the highest levels of M. a. paratuberculosis responsive CD8+ lymphocytes in the circulation about 1-year post-inoculation had no detectable lesions in the distal ileum and colon at necropsy, while high numbers of gammadelta T-cells responsive to M. a. paratuberculosis in the circulation were associated with disseminated lesions in the distal ileum and colon.
用副结核分枝杆菌山羊分离株对山羊进行实验性口服感染,以研究感染亚临床阶段的免疫和细菌学事件。7只5至8周龄的山羊每周三次用代乳品中的细菌悬液投喂,持续9周。6只动物作为对照。通过淋巴细胞增殖试验、干扰素-γ检测和白细胞介素-2受体检测分析针对副结核分枝杆菌的细胞回忆反应。所有接种动物在接种后9周直至2年的研究期间都有可检测到的细胞介导免疫反应,尽管反应在第一年最高。7只动物中有4只在第15至20周可检测到抗副结核分枝杆菌抗体,另有1只动物在第35周抗体呈阳性,而2只接种动物在实验期间未产生显著抗体滴度。接种后约1年,2只动物开始排菌,另外2只在接种后约2年开始向粪便中排泄细菌。就目前用于测量细胞介导免疫的方法所能评估的情况而言,粪便中副结核分枝杆菌的出现与细胞反应的下降无关。在5只动物的肠道和/或肠系膜淋巴结中记录到了由副结核分枝杆菌感染引起的病理病变以及细菌的存在,而在1只动物中观察到了提示副结核的淋巴结变化。只有在尸检时没有活动性感染迹象的2只动物在研究的最后一年细胞参数有相当程度的下降,特别是在干扰素-γ检测中。接种后约1年循环中副结核分枝杆菌反应性CD8 +淋巴细胞水平最高的2只动物在尸检时回肠末端和结肠未检测到病变,而循环中对副结核分枝杆菌反应的γδT细胞数量较多与回肠末端和结肠的播散性病变有关。