2006 Fiscal Year Final Research Report Summary
Role of Interleukin in CD8^+T Cell contraction during Primary Infection
| Project/Area Number |
17590438
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Gunma University |
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Principal Investigator |
YAJIMA Toshiki Gunma University, Faculty of Medicine, Research Associate, 医学部, 助手 (20346852)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAI Yasunobu Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (90158402)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Infectious disease / Immunology / Bacteria |
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| Research Abstract |
During the course of acute infection with an intracellular pathogen, Ag-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. Although IL-15 is known to play an important role in long-term maintenance of memory CD8^+ T cells, the potential roles of IL-15 in CD8^+ T cell contraction are not known. Using an adoptive transfer system of OT-I cells expressing OVA_<257-264>/K^b-specific TCR into control, IL-15 knockout (KO) and IL-15 transgenic (Tg) mice followed by challenge with recombinant Listeria monocytogenes expressing OVA, we found that the survival of CD44+CD62L-CD127- effector OT-I cells during the contraction phase is critically dependent on IL-15. In correlation with the expression level of Bcl-2 in OT-I cells, the number of OT-I cells was markedly reduced in IL-15 KO mice but remained at a high level in IL-15 Tg mice during the contraction phase, compared with control mice. In vivo administration of rIL-15 during the contraction phase in IL-15 KO mice inhibited the contraction of effector OT-I cells accompanied by up-regulation of Bcl-2 expression. Furthermore, enforced expression of Bcl-2 protected the majority of effector OT-I cells from death in IL-15 KO mice after infection. These results suggest that IL-15 plays a critical role in protecting effector CD8^+ T cells from apoptosis during the contraction phase following a microbial infection via inducing antiapoptotic molecules.
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