Yamasaki T, Kikuchi H, Yamashita J, Ljunggren H G, Karre K, Klein G
Department of Neurosurgery, Kyoto University Medical School.
No Shinkei Geka. 1989 Aug;17(8):717-23.
The authors have investigated intracerebral natural resistance mechanism after tumor transplantation into the brain, by using YAC-1 (Moloney leukemia virus-induced T cell lymphoma of A/Sn mouse origin) and its H-2 negative A. H-2-. It was found that highly immunogenic H-2+ YAC-1 was less tumorigenic than A. H-2- in untreated as well as NK-depleted syngeneic mice. The variant cells were not rejected even if inoculated together with YAC-1 cells into the brain. Furthermore, in T cell-depleted, thymectomized mice YAC-1 was as tumorigenic as A. H-2-. Thus, intracerebral natural resistance was expressed against YAC-1, suggesting that T cells but not NK cells might be involved in the tumor rejection with an MHC-restricted regulation. Contrary to this, A. H-2- cells escaped from the natural resistance of the brain. In vitro cytotoxicity assays showed that in relation to the enhancement of cell surface H-2 antigens, intracerebrally passaged YAC-1 cells decreased and increased the sensitivity to NK- and CTL-mediated lysis, respectively. In contrast, A. H-2- did not alter either susceptibility to cell-mediated lysis or cell surface H-2 expression. In vivo rapid elimination assays revealed that after intravenous or subcutaneous inoculation there was a more efficient abrogation of 125I-iododeoxyuridine (IUdR) labelled YAC-1 cells in normal untreated mice compared to NK-depleted mice. After intracerebral inoculation, however, no difference in remaining radioactivity was observed between untreated and NK-depleted mice. This indicates that selective NK-mediated elimination of tumor cells might occur after intravenous or subcutaneous but not after intracerebral inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)
作者通过使用YAC-1(源自A/Sn小鼠的莫洛尼白血病病毒诱导的T细胞淋巴瘤)及其H-2阴性的A.H-2-,研究了肿瘤移植到脑内后的脑内天然抵抗机制。研究发现,在未处理的以及NK细胞缺失的同基因小鼠中,具有高免疫原性的H-2+ YAC-1的致瘤性低于A.H-2-。即使将变异细胞与YAC-1细胞一起接种到脑内,变异细胞也不会被排斥。此外,在T细胞缺失、胸腺切除的小鼠中,YAC-1的致瘤性与A.H-2-相同。因此,脑内对YAC-1表现出天然抵抗,这表明T细胞而非NK细胞可能参与了具有MHC限制调节的肿瘤排斥反应。与此相反,A.H-2-细胞逃避了脑的天然抵抗。体外细胞毒性试验表明,随着细胞表面H-2抗原的增强,脑内传代的YAC-1细胞对NK细胞和CTL介导的裂解的敏感性分别降低和增加。相比之下,A.H-2-对细胞介导的裂解的敏感性或细胞表面H-2表达均未改变。体内快速清除试验显示,静脉内或皮下接种后,与NK细胞缺失的小鼠相比,正常未处理的小鼠中125I-碘脱氧尿苷(IUdR)标记的YAC-1细胞的清除效率更高。然而,脑内接种后,未处理的小鼠和NK细胞缺失的小鼠之间在剩余放射性方面未观察到差异。这表明静脉内或皮下接种后可能发生选择性NK细胞介导的肿瘤细胞清除,但脑内接种后不会发生。(摘要截断于250字)