Maruo K, Shimamura K, Hioki K, Itoh M, Ueyama Y, Tamaoki N
Central Institute for Experimental Animals, Kanagawa, Japan.
APMIS. 1993 May;101(5):345-52. doi: 10.1111/j.1699-0463.1993.tb00120.x.
In order to elucidate the factors influencing the takes of human tumor xenografts in nude mice, we compared the transplantability of human tumors in nude mice with additional genetic defects in the immune system. The nude mice strains tested were classified as follows by expression of the beige gene and the x-linked immunodeficiency (xid) gene: 1) high NK nude (C57BL/6N, nu/nu), 2) low NK nude (C57BL/6 bg/bg nu/nu), 3) high NK nude with B-cell defect (CBA/N nu/nu), and 4) low NK nude with B-cell defect (NIH(S)III). Takes of human tumor xenografts including gastric carcinoma, T-cell lymphoma and B-cell lymphoma were better in nude mice with xid (CBA/N and NIH(S) III nude mice) than in nude mice without xid (B6 and beige nude mice). In addition, among the nude mice with xid expression, the takes were slightly better in nude mice with a CBA/N background than in those with a NIH(S) background. Moreover, the xenotransplantation rate in (CBA/N x C57BL/6N)F1 male nude mice with xid expression was higher than in (C57BL/6N x CBA/N)F1 males without xid expression, but did not react the same level as that in CBA/N nude. On the other hand, introduction of the beige gene into nude mice minimally improved the takes of human tumor xenografts under limited experimental conditions (inoculation of 100 x 10(5) T-cell lymphoma and 1 x 10(5) gastric carcinoma cells) despite the reduction of NK activity. In xenotransplantation of human tumors directly from patients, the take rates of the tumors were also better in CBA/N nude mice than in BALB/cA nude mice. The results in the present report confirmed the effect of xid and CBA/N genetic background on human tumor xenografts in nude mice, suggesting the existence of serum factors, possibly present in serum IgM, mediating rejection of the xenografts.
为了阐明影响人肿瘤异种移植在裸鼠体内成瘤的因素，我们比较了人肿瘤在免疫系统存在额外基因缺陷的裸鼠体内的移植能力。所测试的裸鼠品系根据米色基因和X连锁免疫缺陷（xid）基因的表达情况分类如下：1）高自然杀伤细胞活性裸鼠（C57BL/6N，nu/nu），2）低自然杀伤细胞活性裸鼠（C57BL/6 bg/bg nu/nu），3）伴有B细胞缺陷的高自然杀伤细胞活性裸鼠（CBA/N nu/nu），4）伴有B细胞缺陷的低自然杀伤细胞活性裸鼠（NIH(S)III）。包括胃癌、T细胞淋巴瘤和B细胞淋巴瘤在内的人肿瘤异种移植在具有xid的裸鼠（CBA/N和NIH(S)III裸鼠）体内的成瘤情况比在没有xid的裸鼠（B6和米色裸鼠）体内更好。此外，在具有xid表达的裸鼠中，具有CBA/N背景的裸鼠的成瘤情况略优于具有NIH(S)背景的裸鼠。而且，具有xid表达的（CBA/N×C57BL/6N）F1雄性裸鼠的异种移植率高于没有xid表达的（C57BL/6N×CBA/N）F1雄性裸鼠，但未达到CBA/N裸鼠的相同水平。另一方面，在有限的实验条件下（接种100×10⁵个T细胞淋巴瘤细胞和1×10⁵个胃癌细胞），将米色基因导入裸鼠，尽管自然杀伤细胞活性降低，但对人肿瘤异种移植的成瘤情况改善极小。在直接将患者的人肿瘤进行异种移植时，CBA/N裸鼠体内肿瘤的成瘤率也高于BALB/cA裸鼠。本报告中的结果证实了xid和CBA/N基因背景对人肿瘤在裸鼠体内异种移植的影响，表明可能存在于血清IgM中的血清因子介导了异种移植的排斥反应。
