Association between cell-death induction and pathogenesis in early phase of HIV infection in humanized mice
Project/Area Number |
17K08800
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Experimental pathology
|
Research Institution | National Institute of Infectious Diseases |
Principal Investigator |
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | HIV / T細胞 / ヒト化マウス / 細胞死 / アポトーシス / パイロトーシス / ネクロプトーシス / CD4陽性T細胞 / ナイーブ / メモリー / 休止期 / 潜伏感染 / Flt3-L / GM-CSF / 制御性T細胞 / Th17 |
Outline of Final Research Achievements |
Although transient loss of CD4 T cells occurs during early HIV infection, it remains unclear the characteristics of induced cell death and their relevance to immunopathogenesis. In this study, CD4 T-cell death was characterized during the early phase of HIV-infected humanized mice. As a result, CD4 T-cell death was significantly induced at 3 days post-infection in the spleen, and the main body of induced CD4 T-cell death was non-apoptotic cell death including pyroptosis and necroptosis but not apoptosis. These results suggest a relevance between non-apoptotic CD4 T-cell death and immunopathogenesis such as induction of inflammation.
|
Academic Significance and Societal Importance of the Research Achievements |
現在世界的に行われている抗HIV療法は、ウイルス複製を抑え込みながら細胞死を抑制するのと同時に、宿主本来の免疫恒常性によってCD4 T細胞数の回復を可能にする。そして、さらなる効果的な治療戦略として、感染早期に誘導される細胞死を防ぐ手段も提案されている。しかしながら、どのような様式の細胞死が誘導されるのかについては明らかになっていない。したがって、本研究で得られた知見は臨床応用に向けた論理基盤を確立する上で意義深いものと考えられる。
|
Report
(4 results)
Research Products
(7 results)