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对裸鼠、CD4基因敲除小鼠和严重联合免疫缺陷(SCID)突变小鼠对鼠艾滋病缺陷病毒所致疾病易感性的研究。

Studies of the susceptibility of nude, CD4 knockout, and SCID mutant mice to the disease induced by the murine AIDS defective virus.

作者信息

Simard C, Klein S J, Mak T, Jolicoeur P

机构信息

Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Quebec, Canada.

出版信息

J Virol. 1997 Apr;71(4):3013-22. doi: 10.1128/JVI.71.4.3013-3022.1997.

Abstract

Murine AIDS (MAIDS) is induced by a defective retrovirus that infects lymphocyte cells of the B lineage. To determine whether functional T cells are required for the infection of B cells, T-cell-deficient mice (nude, CD4 knockout, and SCII)) were infected with helper-free stocks of the MAIDS defective virus. Infection of B cells was monitored by Northern blot analysis and in situ hybridization. The C57BL/6 nude mice contained clusters of infected B cells, but less so than did the euthymic mice. In contrast, the (C57BL/6 x BALB/c)F1 nude mice harbored more infected B cells than did their euthymic littermates when maintained in a pathogen-free environment. Clusters of infected B cells were also detected in the MAIDS virus-infected CD4-/- knockout mice despite the total absence of CD4+ T cells in these mice. However, infected cells were not detected in SCID mice (deficient in mature T and B cells) inoculated with the same virus, indicating that precursor B cells are not a target of the virus in the absence of mature CD4+ T cells. These data confirm that the primary event in the development of MAIDS is the infection of relatively mature peripheral B cells and that CD4+ T cells are required to promote the expansion of these infected B cells.

摘要

鼠类获得性免疫缺陷综合征(MAIDS)由一种缺陷型逆转录病毒引起,该病毒感染B淋巴细胞系的细胞。为了确定B细胞感染是否需要功能性T细胞,将T细胞缺陷小鼠(裸鼠、CD4基因敲除小鼠和严重联合免疫缺陷小鼠)用不含辅助病毒的MAIDS缺陷病毒株感染。通过Northern印迹分析和原位杂交监测B细胞的感染情况。C57BL/6裸鼠含有感染B细胞簇,但比正常胸腺小鼠中的少。相比之下,当饲养在无病原体环境中时,(C57BL/6×BALB/c)F1裸鼠体内的感染B细胞比其正常胸腺同窝小鼠更多。在MAIDS病毒感染的CD4-/-基因敲除小鼠中也检测到了感染B细胞簇,尽管这些小鼠中完全没有CD4+T细胞。然而,在用相同病毒接种的严重联合免疫缺陷小鼠(缺乏成熟T细胞和B细胞)中未检测到感染细胞,这表明在没有成熟CD4+T细胞的情况下,前体B细胞不是该病毒的靶标。这些数据证实,MAIDS发展过程中的主要事件是相对成熟的外周B细胞的感染,并且需要CD4+T细胞来促进这些感染B细胞的扩增。

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