Makino M, Chattopadhyay S K, Hartley J W, Morse H C
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1992 Sep 1;149(5):1702-6.
The mixture of retroviruses termed LP-BM5 murine leukemia virus (MuLV) contains a replication-defective genome (BM5def), the crucial element for induction of murine AIDS (MAIDS), as well as helper B-tropic ecotropic and mink cell focus-forming MuLV. Among Fv-1b mouse strains, C57BL mice are sensitive to infection by these viruses and to development of MAIDS, but A/J mice are highly resistant to all viral components and to induction of disease. Inasmuch as previous genetic studies indicated a major role in susceptibility for the H-2D locus within the MHC, the effect of CD8+ T cells in A/J resistance to MAIDS was analyzed by depletion of this subset using mAb. A/J mice treated with anti-CD8 mAb beginning soon after inoculation with LP-BM5 MuLV developed disease within 5 wk after virus inoculation. Histopathologic and flow cytometry alteration of tissues and cells from the mAb-treated mice were identical to those seen in virus-infected MAIDS-sensitive strains, and assays for MuLV demonstrated high-level expression of ecotropic MuLV and integration of BM5def. Parallel studies of A/J mice treated with anti-CD4 mAb after infection revealed enhanced expression of ecotropic MuLV but no integration of BM5def, and no signs of MAIDS were detected. These observations indicate that CD8+ T cells are critical in the resistance of A/J mice to LP-BM5 MuLV replication and development of disease and suggest that CD4+ T cells play a role in regulation of ecotropic virus replication.
被称为LP - BM5鼠白血病病毒（MuLV）的逆转录病毒混合物包含一个复制缺陷型基因组（BM5def），这是诱导鼠类获得性免疫缺陷综合征（MAIDS）的关键因素，以及辅助性嗜B细胞亲嗜性和水貂细胞集落形成性MuLV。在Fv - 1b小鼠品系中，C57BL小鼠对这些病毒的感染以及MAIDS的发展敏感，但A/J小鼠对所有病毒成分以及疾病诱导具有高度抗性。鉴于先前的遗传学研究表明主要组织相容性复合体（MHC）中的H - 2D基因座在易感性中起主要作用，通过使用单克隆抗体（mAb）耗尽该亚群来分析CD8 + T细胞在A/J小鼠对MAIDS抗性中的作用。在接种LP - BM5 MuLV后不久开始用抗CD8 mAb治疗的A/J小鼠在病毒接种后5周内出现疾病。来自mAb治疗小鼠的组织和细胞的组织病理学和流式细胞术改变与在病毒感染的MAIDS敏感品系中观察到的相同，并且对MuLV的检测显示亲嗜性MuLV的高水平表达和BM5def的整合。对感染后用抗CD4 mAb治疗的A/J小鼠的平行研究显示亲嗜性MuLV的表达增强但没有BM5def的整合，并且未检测到MAIDS的迹象。这些观察结果表明CD8 + T细胞在A/J小鼠对LP - BM5 MuLV复制和疾病发展的抗性中起关键作用，并表明CD4 + T细胞在亲嗜性病毒复制的调节中起作用。
