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感染淋巴细胞性脉络丛脑膜炎病毒的免疫活性小鼠肿瘤易感性增强。

Enhanced tumor susceptibility of immunocompetent mice infected with lymphocytic choriomeningitis virus.

作者信息

Kohler M, Rüttner B, Cooper S, Hengartner H, Zinkernagel R M

机构信息

Laboratory of Experimental Pathology, University of Zurich, Switzerland.

出版信息

Cancer Immunol Immunother. 1990;32(2):117-24. doi: 10.1007/BF01754208.

Abstract

Mice infected i.v. with high doses of lymphocytic choriomeningitis virus (LCMV; 10(5)-10(6) plaque-forming units) 8-10 days prior to challenge with the methylcholanthrene-induced fibrosarcoma tumor cell line MC57G or the melanoma cell line B16 tumor cells showed an enhanced tumor susceptibility with respect to both growth kinetics of the tumor and the minimal dose necessary for tumor take. After transient initial growth, MC57G tumor cells were all rejected by uninfected C57BL/6 mice by day 14. Mice preinfected i.v. with LCMV 3 weeks before or at the time of tumor challenge, but not those infected 2 months before or 7 days after, showed increasing tumor growth, the tumor take being 100% for 10(6), 50% for 10(5) and 37% for 10(4) MC57G tumor cells injected into the footpad compared with resistance to 10(6) cells in normal mice. B16 melanoma cells also grew more rapidly in LCMV-preinfected mice and by day 40 tumors were established with about 100 times fewer cells, i.e. about 10(3) compared with 3 x 10(4)-3 x 10(5) for uninfected mice. Analysis of the growth of tumor cells in normal and in LCMV-carrier mice revealed that the latter mice were not more susceptible to LCMV-infected than to uninfected MC57G. Since LCMV-carrier mice fail to mount LCMV-specific T cell responses, these results suggest that anti-LCMV-specific T cells may be responsible for acquired immunodeficiency hampering immune surveillance against the tumors studied.

摘要

在以甲基胆蒽诱导的纤维肉瘤肿瘤细胞系MC57G或黑色素瘤细胞系B16肿瘤细胞进行攻击前8 - 10天,经静脉注射高剂量淋巴细胞性脉络丛脑膜炎病毒(LCMV;10000 - 1000000蚀斑形成单位)感染的小鼠,在肿瘤生长动力学和肿瘤接种所需的最小剂量方面均表现出更高的肿瘤易感性。短暂的初始生长后,未感染的C57BL/6小鼠在第14天会排斥所有MC57G肿瘤细胞。在肿瘤攻击前3周或攻击时经静脉注射LCMV预感染的小鼠,而非在攻击前2个月或攻击后7天感染的小鼠,肿瘤生长有所增加,与正常小鼠对1000000个细胞的抗性相比,注射到足垫的100000个MC57G肿瘤细胞的肿瘤接种率为100%,10000个为50%,1000个为37%。B16黑色素瘤细胞在LCMV预感染的小鼠中也生长得更快,到第40天时,肿瘤形成时所需的细胞数量约少100倍,即约1000个,而未感染小鼠则需要30000 - 300000个。对正常小鼠和LCMV携带小鼠中肿瘤细胞生长的分析表明,后一组小鼠对LCMV感染的MC57G并不比未感染的更易感。由于LCMV携带小鼠无法产生LCMV特异性T细胞反应,这些结果表明,抗LCMV特异性T细胞可能是导致获得性免疫缺陷从而妨碍对所研究肿瘤进行免疫监视的原因。

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