Taylor Matthew D, Else Kathryn J
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh and School of Biological Sciences, University of Manchester, Manchester, UK.
Parasite Immunol. 2002 Jan;24(1):1-13. doi: 10.1046/j.0141-9838.2001.00435.x.
Trichuris trichiura is a highly prevalent intestinal helminth of humans with a well-characterized animal model, Trichuris muris in the mouse. Relating the murine work back to the human infection has been difficult, however, as many of the questions addressed in the mouse cannot be asked in humans. The ability to reconstitute a mouse with a human immune system could help bridge this gap, allowing a human immune response to be studied under a controllable laboratory environment. In this study, we demonstrate that severe combined immunodeficient mice engrafted with naïve human peripheral blood lymphocytes are capable of mounting a Trichuris specific human antibody response after vaccination with T. muris antigens. The phenotype of the response depended on the vaccinating antigen with excretory/secretory antigens eliciting a human immunoglobulin IgG2 response, and whole worm homogenate stimulating IgG1 and IgG2 responses. Vaccination with homogenate also enhanced a human IgG response against a 66-kDa component of T. muris homogenate in a donor-dependent manner. This work shows the potential of using the humanized mouse model for studying the immune responses of humans living in T. trichiura endemic areas.
毛首鞭形线虫是一种在人类中高度流行的肠道蠕虫，在小鼠中有一个特征明确的动物模型——鼠鞭虫。然而，将小鼠实验的成果应用于人类感染情况一直很困难，因为许多在小鼠中研究的问题无法在人类身上进行探究。用人免疫系统重建小鼠的能力有助于弥合这一差距，从而能够在可控的实验室环境中研究人类免疫反应。在本研究中，我们证明，植入未接触过抗原的人外周血淋巴细胞的重度联合免疫缺陷小鼠，在用鼠鞭虫抗原接种疫苗后，能够产生针对鞭虫的特异性人类抗体反应。反应的表型取决于接种的抗原，排泄/分泌抗原引发人类免疫球蛋白IgG2反应，而全虫匀浆刺激IgG1和IgG2反应。用匀浆接种疫苗还以依赖供体的方式增强了人类针对鼠鞭虫匀浆66 kDa成分的IgG反应。这项工作展示了使用人源化小鼠模型研究生活在毛首鞭形线虫流行地区人群免疫反应的潜力。
