Analysis for the pathogenesis of concomitant infection in AIDS and murine AIDS

艾滋病及小鼠艾滋病合并感染的发病机制分析

基本信息

批准号：
10045068
负责人：
YOSHIKAI Yasunobu
金额：
$ 2.05万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10045068/
关键词：
MAIDS Mycobacteria host defense IL-15 transgenic mice memory CD8 T cells NK cells γδT cells 複合感染 Th1細胞 IL-15トランスジェニックマウスメモリーCD8T細胞

项目摘要

LP-BM5 murine leukemia virus (MuLV) injection is a causative of murine AIDS (MAIDS), characterized by a variety of functional abnormalities of immunocompetent cells and susceptibility to various infectious with Mycobacterium avium or M. bovis BCG as assessed by survival rate and bacterial counts. The expression of IL-15 in the peritoneal macrophages was severely impaired in MAIDS mice following infection with M. bovis BCG. NK cells were increased in the peritoneal cavity of normal mice at earl stage after BCG infection, whereas such increases were not evident in MAIDS mice. Serum IFN-γ level was also depressed in MAIDS mice following BCG infection. The production IFN-γ by T cells from the MAIDS mice infected with M. bovis BCG was significantly lower in response to PPD than that of normal mice infected with M. bovis BCG. These results suggested that depressed IL-15 production in MAIDS mice might be involved in susceptibility against M. bovis BCG.To elucidate the protective roles of IL-15 in the progression of MAIDS, we constructed transgenic mice using IL-15 cDNA under the control of an MHC class I promoter. The IL-15 Tg mice constitutionally produced a significant level of IL-15 protein and had markedly increased numbers of memory type (CD44ィイD1highィエD1 Ly6CィイD1+ィエD1) of CD8ィイD1+ィエD1T cells in the LN. These mice showed resistance to LP-BM5 infection accompanied by increases in NK cells and memory CD8ィイD1+ィエD1 T cells and enhanced IFN-γ production. Thus, these findings suggest that IL-15 production is partly responsible for MAIDS progression and that IL-15 may be protective for MAIDS and presumably AIDS progression.

LP-BM5鼠白血病病毒（MULV）注射是对鼠艾滋病（MIADS）的一种原因，其特征是免疫能力细胞的各种功能异常，并且对各种感染性aviavis and M. bcg的感染性易感性，如生存率和细菌率所评估。在牛乳杆菌BCG感染后，女仆小鼠中IL-15在腹膜巨噬细胞中的表达严重受损。 BCG感染后早期正常小鼠的腹膜腔中增加了NK细胞，而在女仆小鼠中没有证明这种增加。 BCG感染后，女仆小鼠的血清IFN-γ水平也降低。对PPD感染的女仆小鼠的T细胞产生的IFN-γ显着低于感染牛乳杆菌BCG的正常小鼠。这些结果表明，女仆中的IL-15产生抑郁症可能参与了针对Bovis BCG的敏感性，以阐明IL-15在女仆进展中的受保护作用，我们使用IL-15 cDNA在MHC I类启动子的控制下构建了转基因小鼠。 IL-15 TG小鼠的一致性产生了显着水平的IL-15蛋白，并显着增加了LN中CD8 D1+ D1T细胞的记忆类型（CD44 D1 Highie D1 LY6 CII D1+ D1）。这些小鼠表现出对NK细胞和记忆CD8 D1+ D1 T细胞增加并增强IFN-γ产生的抗LP-BM5感染的抗性。这是这些发现表明，IL-15的产生是女仆进展的部分原因，并且可以保护IL-15的女仆，并可能有助于进展。