Shibata S, Asano T, Noguchi A, Kimura H, Ogura A, Naiki M, Doi K
Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo, Japan.
Cell Immunol. 1998 Jan 10;183(1):60-9. doi: 10.1006/cimm.1997.1238.
To improve the engraftment of human peripheral blood lymphocytes (PBL) to severe combined immunodeficient (SCID) mice, and to elucidate the factors which prevent the PBL's survival, we treated SCID mice with mAb, which neutralizes murine IFN-gamma's ability to activate cell-mediated immunity. Compared with untreated mice, mAb-treated mice retained significantly higher numbers and ratios of human PBL in the peritoneal cavity and spleen, as well as significantly higher serum titers of human IgG and IgM. Histologically, host versus graft reaction (HVGR) was less severe in the mAb-treated mice. Moreover, these phenomena were completely abrogated when mice were also treated with murine recombinant IFN-gamma. These results suggest that murine IFN-gamma plays an important role in the rejection of human cells in SCID mice and that its depletion by means of mAb treatment can significantly reduce HVGR and improve the engraftment of human PBL.
为提高人类外周血淋巴细胞(PBL)在重症联合免疫缺陷(SCID)小鼠体内的植入率,并阐明阻碍PBL存活的因素,我们用单克隆抗体(mAb)处理SCID小鼠,该单克隆抗体可中和小鼠干扰素-γ激活细胞介导免疫的能力。与未处理的小鼠相比,经mAb处理的小鼠腹腔和脾脏中人类PBL的数量和比例显著更高,血清中人IgG和IgM的滴度也显著更高。组织学检查显示,经mAb处理的小鼠中宿主抗移植物反应(HVGR)较轻。此外,当小鼠同时用小鼠重组干扰素-γ处理时,这些现象完全消失。这些结果表明,小鼠干扰素-γ在SCID小鼠排斥人类细胞的过程中起重要作用,通过mAb处理去除该干扰素可显著降低HVGR并提高人类PBL的植入率。