Tournoy K G, Depraetere S, Meuleman P, Leroux-Roels G, Pauwels R A
University Hospital Gent, Department of Respiratory Diseases, Belgium.
Eur J Immunol. 1998 Oct;28(10):3221-30. doi: 10.1002/(SICI)1521-4141(199810)28:10<3221::AID-IMMU3221>3.0.CO;2-S.
Severe combined immunodeficient (SCID) mice accept human xenografts and can act as a model for human immune functions. Murine natural killer cells (NK), however, represent an important barrier for the reconstitution of SCID mice with human peripheral blood leukocytes (Hu-PBL). We investigated the effect on Hu-PBL survival of pretreatment with TM-beta1, a rat monoclonal antibody for the mouse IL-2 receptor beta chain. TM-beta1 greatly improved the survival of Hu-PBL. Human lymphocytes, predominantly T cells, survived in the peritoneum and infiltrated spleen and lungs already 1 week after engraftment and liver and thymus from 2 weeks on. Secondary humoral responses were evaluated with Hu-PBL from a donor immune to hepatitis-B surface Ag (HBsAg) and tetanus toxoid (TT). TM-beta1 pretreatment enhanced the recall Ig response to HBsAg and did not affect the baseline anti-TT Ig production. In conclusion, TM-beta1 pretreatment of SCID mice significantly improves the survival and functionality of the Hu-PBL graft.
重症联合免疫缺陷(SCID)小鼠可接受人类异种移植,可作为人类免疫功能的模型。然而,小鼠自然杀伤细胞(NK)是用人外周血白细胞(Hu-PBL)重建SCID小鼠的一个重要障碍。我们研究了用TM-β1(一种针对小鼠白细胞介素-2受体β链的大鼠单克隆抗体)预处理对Hu-PBL存活的影响。TM-β1大大提高了Hu-PBL的存活率。人淋巴细胞,主要是T细胞,在植入后1周即在腹膜内存活,并浸润脾脏和肺,从2周起浸润肝脏和胸腺。用对乙型肝炎表面抗原(HBsAg)和破伤风类毒素(TT)免疫的供体的Hu-PBL评估二次体液反应。TM-β1预处理增强了对HBsAg的回忆性Ig反应,且不影响基线抗TT Ig的产生。总之,对SCID小鼠进行TM-β1预处理可显著提高Hu-PBL移植物的存活率和功能。