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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小鼠白血病病毒(MuLV)注射是引起小鼠艾滋病(MAIDs)的一种病原体，其特征是免疫活性细胞的各种功能异常和对各种感染性疾病的敏感性，以存活率和细菌计数为评价指标。乳鼠感染卡介苗后，巨噬细胞中IL-15的表达严重受损。正常小鼠感染卡介苗后早期，其腹腔液中的NK细胞明显增加，而未感染的小鼠则未见明显增加。卡介苗感染后，乳鼠血清中干扰素-γ水平也明显降低。卡介苗感染乳鼠的T细胞产生干扰素-γ的能力明显低于感染卡介苗的正常小鼠。为了阐明IL-15在家系发育过程中的保护作用，我们在MHC-I类启动子的控制下构建了IL-15的转基因小鼠。IL-15TG小鼠体内产生明显的IL-15蛋白，并显著增加LN内CD8CD8D1HIGHィイD1LY6CィエD1D1CD8CD1D1T细胞的记忆类型(CD44CD8D1HighィエD1Ly6CCDD1+CD8D1T细胞)。这些小鼠表现出对LP-BM5感染的抵抗力，并伴有NK细胞和记忆性CD8、ィイD1+ィエD1T细胞的增加和干扰素-γ产生的增加。因此，这些发现表明，IL-15的产生在一定程度上导致了女佣的进展，并且IL-15可能对女佣和可能的艾滋病进展具有保护作用。