| Project/Area Number |
13226036
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
| Allocation Type | Single-year Grants |
|---|
| Review Section |
Biological Sciences
|
|---|
| Research Institution | Kyushu University (2002-2005)
Nagoya University (2001) |
|---|
Principal Investigator |
YOSHIKAI Yasunobu Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (90158402)
|
|---|
| Project Period (FY) |
2001 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥60,600,000 (Direct Cost: ¥60,600,000)
Fiscal Year 2005: ¥16,500,000 (Direct Cost: ¥16,500,000)
Fiscal Year 2004: ¥16,500,000 (Direct Cost: ¥16,500,000)
Fiscal Year 2003: ¥17,600,000 (Direct Cost: ¥17,600,000)
Fiscal Year 2002: ¥10,000,000 (Direct Cost: ¥10,000,000)
|
|---|
| Keywords | IL-15 / memory CD8 T cells / apoptosis / Listeria / homeostatic proliferation / reactivation / 再感染 / 2次免疫応答 / グランザイム / 細胞分裂 / 感染防御 / 細胞傷害活性 / 肝傷害 / IL-15トランスジェニックマウス / IL-15ノックアウトマウス / Listeria monocytogene / BCG / Listeria monocytogeness / エフェクターT細胞 / メモリーT細胞 / H2M3テトラマー / L.monocytogenes / トランスジェニックマウス / Bcl-2 |
|---|
| Research Abstract |
During the course of acute infection with an intracellular pathogen, antigen-specific T cells proliferate in the expansion phase, and then most of the T cells die by apoptosis in the following contraction phase, but the few that survive become memory cells and persist for a long period of time. Memory CD8T cells are activated rapidly against re-infection and eliminate pathogens. Using an adoptive transfer system of OT-I cells expressing OVA_<257-264>/K^b-specific T cell receptor into control, IL-15 knockout (KO) and IL-15 transgenic (Tg) mice followed by challenge with recombinant Listeria monocytogenes expressing OVA, we found the roles of IL-15 in generation, maintenance and reactivation of memory CD8T cells as follows :
(1) Effector phase : IL-15 is dispensable for generation of effector CD8T cells following bacterial infection.
(2) Contraction phase : IL-15 plays a critical role in protecting effector CD8^+T cells from apoptosis during the contraction phase following a microbial infection via inducing anti-apoptotic molecules.
(3) Maintenance phase : IL-15 plays an important role in long-term maintenance of memory CD8^+ T cells through induction of homeostatic proliferation.
(4) Reactivation : IL-15 plays an important role in early activation of memory CD8^+ T cells through induction of cytotoxic molecules upon re-infection.
|
