| Project/Area Number |
10045068
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B).
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Virology
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
YOSHIKAI Yasunobu Nagoya University, School of Medicine, Professor, 医学部, 教授 (90158402)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Hitoshi School of Medicine, Research Associate, 医学部, 助手 (00283440)
WORAWIDH Waj カセサート大学, 獣医学部, 助教授
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
|---|
| Keywords | 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 |
|---|
| Research Abstract |
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.
|
