B and T cells are required for mouse mammary tumor virus spread within the mammary gland.

B and T cells are required for mouse mammary tumor virus spread within the mammary gland.
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DOI:
10.4049/jimmunol.161.5.2375
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发表时间:
1998-09
影响因子:
4.4
通讯作者:
T. Golovkina;J. Dudley;S. Ross
T. Golovkina;J. Dudley;S. Ross
中科院分区:
医学2区
文献类型:
--
作者:
T. Golovkina;J. Dudley;S. Ross

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小鼠乳腺肿瘤病毒(MMTV)是一种传染性逆转录病毒,通过乳汁从母亲传播给新生儿。 MMTV 编码一种超级抗原 (SAg),其活性对于病毒的生命周期是不可或缺的,因为带有 sag 基因突变的基因工程病毒既不会在哺乳幼崽的免疫系统细胞中扩增,也不会感染它们的乳腺。当将野生型 MMTV 直接注射到未感染的青春期小鼠的乳腺中时,它们的淋巴和乳腺细胞都被病毒感染。为了测试这种淋巴细胞感染是否依赖于 SAg 活性以及病毒在乳腺内传播所需,我们将野生型 MMTV (C3H) 注射到缺乏 SAg 同源 V beta 14+ T 细胞的两种转基因小鼠品系的乳腺中。 MTV-ORF 或 LEL 菌株均未表现出乳腺感染。此外,未检测到其外周淋巴细胞有MMTV感染。对缺乏 B 细胞(mu 链敲除)的小鼠进行的类似实验显示,在乳腺或淋巴组织中没有检测到病毒传播。这些数据表明,SAg 活性和 MMTV 感染的淋巴细胞不仅对于病毒感染的初始步骤是必需的,而且对于病毒在乳腺内的传播也是必需的。感染后期的病毒传播决定了 MMTV 是否会诱发乳腺肿瘤。
Mouse mammary tumor virus (MMTV) is an infectious retrovirus transmitted through milk from mother to newborns. MMTV encodes a superantigen (SAg) whose activity is indispensable for the virus life cycle, since a genetically engineered virus with a mutation in the sag gene neither amplified in cells of the immune system of suckling pups nor infected their mammary glands. When wild-type MMTV was injected directly into the mammary glands of uninfected pubescent mice, their lymphoid as well as mammary gland cells became virus infected. To test whether this infection of lymphoid cells was dependent on SAg activity and required for virus spread within the mammary gland, we performed mammary gland injections of wild-type MMTV(C3H) into two strains of transgenic mice that lacked SAg-cognate, V beta 14+ T cells. Neither the MTV-ORF or LEL strains showed infection of their mammary glands. Moreover, no MMTV infection of their peripheral lymphocytes was detected. Similar experiments with mice lacking B cells (mu-chain knockouts) showed no detectable virus spread in the mammary glands or lymphoid tissues. These data suggest that SAg activity and MMTV-infected lymphocytes are required, not only for initial steps of viral infection, but also for virus spread within the mammary gland. Virus spread at late times in infection determines whether MMTV induces mammary tumors.