Beaman M H, Remington J S, Meyer D J
University of Western Australia, Nedlands, Australia.
Immunol Cell Biol. 2000 Dec;78(6):608-15. doi: 10.1046/j.1440-1711.2000.00957.x.
Toxoplasmosis is a potentially fatal opportunistic infection of immunocompromised hosts. Improved animal models of toxoplasmosis are needed to more nearly approximate conditions that occur in immunocompromised humans. The development of models of toxoplasmosis using human peripheral blood lymphocytes (hu-PBL) transplanted into severe combined immunodeficiency (SCID) mice is described here. Transplantation of hu-PBL into SCID mice without prior conditioning of the mice resulted in detectable differences in quantitative histological scores of brain inflammation due to Toxoplasma gondii infection, but did not alter mortality when compared to SCID mouse controls. The lack of detectable differences in survival were due to inadequate engraftment of hu-PBL, as assessed by flow cytometry. Unconditioned hu-PBL SCID mice had low titre T. gondii-specific antibody detectable after infection. When pretransplantation conditioning with irradiation and antiasialo GM 1 (n-glucolyl neuraminic acid) antibody was used, prolonged hu-PBL engraftment was observed in SCID mice, which was associated with worsened histopathology and usually impaired survival when compared with SCID mouse controls. When pretransplantation conditioning with irradiation, antiasialo GM antibody and polyethylene glycol-conjugated IL-2 was used, prolonged hu-PBL engraftment was also documented, but this did not affect survival from T. gondii infection when compared with similarly conditioned SCID mouse controls. The latter conditioning protocol resulted in hu-PBL SCID mice producing high titre T. gondii-specific antibody after infection. Conditioned hu-PBL SCID mice had evidence of increased T. gondii-induced inflammatory scores when compared with conditioned SCID mice. These models show promise for the study of the pathogenesis of toxoplasmosis and conditioned hu-PBL SCID mice may have applications for the evaluation of novel therapies for toxoplasmosis in immunocompromised humans.
弓形虫病是免疫功能低下宿主中一种潜在致命的机会性感染。需要改进的弓形虫病动物模型，以更接近免疫功能低下人类所发生的情况。本文描述了使用移植到严重联合免疫缺陷（SCID）小鼠体内的人外周血淋巴细胞（hu-PBL）建立弓形虫病模型的过程。在未对小鼠进行预先预处理的情况下，将hu-PBL移植到SCID小鼠体内，由于刚地弓形虫感染，在脑炎症的定量组织学评分上产生了可检测到的差异，但与SCID小鼠对照组相比，并未改变死亡率。通过流式细胞术评估，存活方面缺乏可检测到的差异是由于hu-PBL植入不足。未预处理的hu-PBL SCID小鼠在感染后可检测到低滴度的弓形虫特异性抗体。当使用照射和抗唾液酸GM1（N-葡糖基神经氨酸）抗体进行移植前预处理时，在SCID小鼠中观察到hu-PBL植入时间延长，这与组织病理学恶化相关，并且与SCID小鼠对照组相比，通常生存受损。当使用照射、抗唾液酸GM抗体和聚乙二醇偶联的IL-2进行移植前预处理时，也记录到hu-PBL植入时间延长，但与同样预处理的SCID小鼠对照组相比，这并未影响刚地弓形虫感染后的存活情况。后一种预处理方案导致hu-PBL SCID小鼠在感染后产生高滴度的弓形虫特异性抗体。与预处理的SCID小鼠相比，预处理的hu-PBL SCID小鼠有证据表明刚地弓形虫诱导的炎症评分增加。这些模型在弓形虫病发病机制研究方面显示出前景，并且预处理的hu-PBL SCID小鼠可能在评估免疫功能低下人类弓形虫病新疗法方面有应用价值。
