2005 Fiscal Year Final Research Report Summary
Molecular mechanisms for generation and maintenance of memory CD8T cells following bacterial infection.
| Project/Area Number |
13226036
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyushu University (2002-2005)
Nagoya University (2001) |
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Principal Investigator |
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) |
2001 – 2005
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| Keywords | IL-15 / memory CD8 T cells / apoptosis / Listeria / homeostatic proliferation / reactivation |
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| 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.
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[Journal Article] Toll-like receptors 2 and 4 are differentially involved in Fas-dependent apoptosis in Peyer's patch and liver at an early stage after bile duct ligation in mice.2006
Author(s)
Ogawa A:, Tagawa T., Nishimura H., Yajima T., Abe T., Arai T., Taniguchi M., Takeda K., Akira S., Nimura Y., Yoshikai Y.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A novel model system for renal cancer treatmant with low levels of mixed chimerism by nonmyeloidablative allogeniec hematopoietic cell transplantation in combination with cyclophosphamide in mice.2005
Author(s)
Harano, M., Eto, M., Iwai T., Tasugami K., Kiyoshima K., Tsuneyoshi, M., Yoshikai Y., Naito S.
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Journal Title
Cancer Res. 65
Pages: 10032-40
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A serine/threonine kinase, Cot/Tp12, modulates bacterial DNA-induced IL-12 production and Th cell differentiation.2004
Author(s)
Sugimoto K, Ohata M, Miyoshi J, Ishizaki H, Tsuboi N, Masuda A, Yoshikai Y, Takamoto M, Sugane K, Matsuo S, Shimada Y, Matsuguchi T.
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Journal Title
J Clin Invest. 114
Pages: 857-66
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] VOP-OT cells producing CC-chemokines may bridge a gap between neutrophils and macrophages in innate immunity during Escherichia coli infection in mice2004
Author(s)
Tagawa, T., Nishimura, H., Yajima, T., Hara, H., Kishihara, K., Matsuzaki, G., Yoshino, I., Maehara, Y., Yoshikai.Y.
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Journal Title
J.Immunol. 105
Pages: 5156-5164
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Soluble branched (1,4)-P-D-glucans from Acetobacter species show strong activities to induce IL-12 in vitro and inhibit Th2 response with IgE production in vivo.2003
Author(s)
Saito K., Yajima T., Nishimura H., Aiba K., Ishimitsu R., Matsuguchi T., Fushim T., Ohshima Y., Tsukamoto Y., Yoshikai Y.
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Journal Title
J. Biol. Chem. 278
Pages: 38571-38578
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Overexpression of IL-15 in vivo Increases antigen-driven memory CD8+T cells following a microbe exposure2002
Author(s)
Yajima, T., Nishimura, H., Ishimitsu, R., Watase, T.,.Busch, D.H, Pamer, E.G., Kuwano, H., Yoshikai, Y.
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Journal Title
J. Immunol. 168
Pages: 1198-203
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Overexpression of interleukin-15 in vivo enhances anti-tumor activity against MHC class I-negative and-positive B16 melanoma throught augmented NK activity or Ag-specific cytotoxic T cell responses.2002
Author(s)
Yajima, T., Nishimura, H., Wajjwalku, W, Harada, M., Kuwano, H., Yoshikai, Y.
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Journal Title
Int.J. Cancer 99
Pages: 573-8
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Toll-like receptor 2 contributes to liver injury induced by Salmonella infection through Fas ligand expression on NKT cells in mice.2002
Author(s)
Shimizu, H., Matsuguchi, T., Fukuda, Nakano, I., Hayakawa, T., Takeuchi, 0., Akira, S., Yoshikai, Y.
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Journal Title
Gastroenterology 123
Pages: 1265-1277
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Overexpression of Interleukin-15 in vivo enhances Tcl response which inhibits allergic inflammation in a murine model of asthma.2001
Author(s)
Ishimitsu, R., Nishimura, H., Yajima, T., Watase, T., Kawauchi, H., Yoshikai, Y.
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Journal Title
J. Immunol. 166
Pages: 1991-2001
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mice lacking IL-2/IL-15 receptor R chain are susceptible but mice lacking IL-2 are resistant to infection with avirulent Salmonella choleraesuis.2001
Author(s)
Nishimura, H., Tagaya, M., Tsunobuchi, H., Suzuki, H., Nakashima, I, Yoshikai, Y
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Journal Title
Infect. Immun. 69
Pages: 1226-1229
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Gene expression of osteoclast differentiation factor is induced by lipopolysaccharide in mouse osteoblasts via TolH-like receptors.2001
Author(s)
Kikuchi, T., Matsuguchi, T., Mitani, A., Tanaka, S., Matsuoka, M., Yamamoto, G., Hishikawa, T., Noguchi, T., Yoshikai, Y.
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Journal Title
J.Immunol. 166
Pages: 3574-3579
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Memory phenotype CD8+T cells increased in IL-15 transgenic mice are involved in early protection against a primary infection with Listeria monocytogenes.2001
Author(s)
Yajima, T., Nishimura, H., Ishimitsu, R., Yamamura, K., Watase, T., D.H.Busch, E.G.Pamer, Kuwano, H., Yoshikai, Y.
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Journal Title
Eur. J. Immunol. 31
Pages: 757-766
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Impaired IL-15 production in murine AIDS mice might uderlie susceptibility to mycobacterial infection.2001
Author(s)
Umemura, M., Wajjwalku, W., Hirose, K., Emoto, M., Nishimura, H., Matsuguchi, T., Gotoh, Y., Takahashi, M., Makino, M., Yoshikai,Y.
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Journal Title
J.Leuko.Biol. 69
Pages: 138-148
Description
「研究成果報告書概要(欧文)」より
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