Naito S, Okada Y, Takahashi M, Kato H, Taneichi M, Ami Y, Suzaki Y, Oka T, Okuma K, Morokuma K, Onodera H, Inoue M, Takahashi Y, Yamazaki S, Kimura H, Komuro K, Uchida T
Department of Safety Research on Biologics, National Institute of Infectious Diseases, Tokyo, Japan.
Int Arch Allergy Immunol. 2000 Oct;123(2):149-54. doi: 10.1159/000024434.
In this study, severe combined immunodeficiency (SCID) mice, which permit the survival of lymphoid cells of human origin, were used to study the human anti-tetanus immune response.
Human peripheral blood lymphocytes (hu-PBL) obtained from 88 healthy donors (aged from 18 to 62) were transplanted into SCID mice, and anti-tetanus toxoid (Ttd) antibody production and protection against lethal doses of tetanus toxin (Ttx) were investigated in the hu-PBL-SCID mice.
The transfer of human PBL evoked significant human anti-Ttd IgG antibody production for 37.5% of the donors. After in vivo immunization, the percentage of donors with PBL exhibiting positive anti-TtD IgG production in the mice increased to 54.5%. Mean anti-Ttd IgG levels in the sera were also significantly elevated in response to immunization. The mean IgG titer for the mice injected with PBL from donors under the age of 40 was significantly higher than that of the mice injected with PBL from donors aged 40 or older. Four weeks after the cell transfer, the mice were challenged with Ttx. The induction of protection against Ttx challenge was observed mostly in mice with PBL transferred from donors under the age of 40. In vivo immunization in SCID mice with Ttd increased the number of cases of resistance to Ttx.
These results suggest that hu-PBL-SCID mice might serve as a tool for predicting the protective ability against pathogens in PBL donors and also for evaluating vaccine efficacy.
在本研究中,使用了能使人类来源的淋巴细胞存活的严重联合免疫缺陷(SCID)小鼠来研究人类抗破伤风免疫反应。
从88名健康供者(年龄在18至62岁之间)获取的人外周血淋巴细胞(hu - PBL)被移植到SCID小鼠体内,然后在hu - PBL - SCID小鼠中研究抗破伤风类毒素(Ttd)抗体的产生以及对致死剂量破伤风毒素(Ttx)的保护作用。
对于37.5%的供者,人PBL的移植引发了显著的人抗Ttd IgG抗体产生。在体内免疫后,小鼠中PBL表现出抗TtD IgG产生阳性的供者比例增加到54.5%。血清中的平均抗Ttd IgG水平也因免疫而显著升高。注射40岁以下供者PBL的小鼠的平均IgG滴度显著高于注射40岁及以上供者PBL的小鼠。细胞移植四周后,用Ttx攻击小鼠。在大多数移植了40岁以下供者PBL的小鼠中观察到了对Ttx攻击的保护作用诱导。在SCID小鼠中用Ttd进行体内免疫增加了对Ttx耐药的病例数。
这些结果表明,hu - PBL - SCID小鼠可能作为一种工具,用于预测PBL供者对病原体的保护能力,也用于评估疫苗效力。