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)注射剂是鼠艾滋病(MAIDS)的病原体，其特征是免疫活性细胞的多种功能异常，并且通过存活率和细菌评估对鸟分枝杆菌或牛分枝杆菌卡介苗的各种感染敏感。 MAIDS 小鼠感染牛分枝杆菌 BCG 后，腹腔巨噬细胞中 IL-15 的表达严重受损。 BCG 感染后早期的正常小鼠腹腔内存在 IFN-γ 水平，而 MAIDS 小鼠的血清 IFN-γ 水平在 BCG 感染后也有所降低。感染牛支原体 BCG 的小鼠对 PPD 的反应显着低于感染牛支原体 BCG 的正常小鼠。这些结果表明，MAIDS 小鼠中 IL-15 产生的抑制可能与对 MAIDS 的易感性有关。为了阐明IL-15在MAIDS进展中的保护作用，我们使用在MHC I类启动子控制下的IL-15 cDNA构建了转基因小鼠。IL-15 Tg小鼠本质上产生显着水平的IL。 -15 蛋白，并且 CD8D1+D1T 细胞的记忆型 (CD44D1highD1 Ly6CD1+D1) 数量显着增加这些小鼠表现出对 LP-BM5 感染的抵抗力，并伴有 NK 细胞和记忆 CD8D1+D1 T 细胞的增加以及 IFN-γ 产生的增强。因此，这些发现表明 IL-15 的产生是 MAIDS 进展的部分原因。 IL-15 可能对 MAIDS 以及艾滋病进展具有保护作用。