Lemke Caitlin D, Haynes Joseph S, Spaete Rodger, Adolphson Deb, Vorwald Ann, Lager Kelly, Butler John E
Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA.
J Immunol. 2004 Feb 1;172(3):1916-25. doi: 10.4049/jimmunol.172.3.1916.
Amid growing evidence that numerous viral infections can produce immunopathology, including nonspecific polyclonal lymphocyte activation, the need to test the direct impact of an infecting virus on the immune system of the host is crucial. This can best be tested in the isolator piglet model in which maternal and other extrinsic influences can be excluded. Therefore, neonatal isolator piglets were colonized with a benign Escherichia coli, or kept germfree, and then inoculated with wild-type porcine reproductive and respiratory syndrome virus (PRRSV) or sham medium. Two weeks after inoculation, serum IgM, IgG, and IgA levels were 30- to 50-, 20- to 80-, and 10- to 20-fold higher, respectively, in animals receiving virus vs sham controls, although <1% was virus specific. PRRSV-infected piglets also had bronchial tree-associated lymph nodes and submandibular lymph nodes that were 5-10 times larger than colonized, sham-inoculated animals. Size-exclusion fast performance liquid chromatography revealed that PRRSV-infected sera contained high-molecular-mass fractions that contained IgG, suggesting the presence of immune complexes. Lesions, inflammatory cell infiltration, glomerular deposits of IgG, IgM, and IgA, and Abs of all three isotypes to basement membrane and vascular endothelium were observed in the kidneys of PRRSV-infected piglets. Furthermore, autoantibodies specific for Golgi Ags and dsDNA could be detected 3-4 wk after viral inoculation. These data demonstrate that PRRSV induces B cell hyperplasia in isolator piglets that leads to immunologic injury and suggests that the isolator piglet model could serve as a useful model to determine the mechanisms of virus-induced immunopathology in this species.
越来越多的证据表明，许多病毒感染会产生免疫病理学现象，包括非特异性多克隆淋巴细胞激活，因此，测试感染病毒对宿主免疫系统的直接影响至关重要。这在隔离仔猪模型中测试效果最佳，因为该模型可排除母体和其他外部影响。因此，将新生隔离仔猪用良性大肠杆菌定殖，或保持无菌状态，然后接种野生型猪繁殖与呼吸综合征病毒（PRRSV）或假培养基。接种两周后，与假对照组相比，接受病毒接种的动物血清IgM、IgG和IgA水平分别高出30至50倍、20至80倍和10至20倍，尽管其中<1%是病毒特异性的。感染PRRSV的仔猪的支气管树相关淋巴结和下颌下淋巴结也比定殖、假接种的动物大5至10倍。尺寸排阻快速高效液相色谱显示，感染PRRSV的血清中含有包含IgG的高分子质量组分，表明存在免疫复合物。在感染PRRSV的仔猪肾脏中观察到病变、炎性细胞浸润、IgG、IgM和IgA的肾小球沉积，以及针对基底膜和血管内皮的所有三种同种型抗体。此外，病毒接种后3至4周可检测到针对高尔基体抗原和双链DNA的自身抗体。这些数据表明，PRRSV在隔离仔猪中诱导B细胞增生，导致免疫损伤，并表明隔离仔猪模型可作为确定该物种中病毒诱导免疫病理学机制的有用模型。
