2001 Fiscal Year Annual Research Report

インターロイキン15によるメモリー型CD8^+T細胞のシグナル伝達機構

Research Project

Project/Area Number	13037017
Research Category	Grant-in-Aid for Scientific Research on Priority Areas (A)
Research Institution	Nagoya University
Principal Investigator	吉開泰信名古屋大学, 大学院・医学研究科, 教授 (90158402)
Keywords	IL-15 / トランスジェニックスマウス / CD8T細胞 / Bcl-2 / 細胞分裂
Research Abstract	本年度はIL-15過剰発現による抗原特異的メモリーCD8^+T細胞の維持機構を解析するとともに、内因性IL-15の産生を抑制した時の抗原特異的CD8^+T細胞の産生へ効果を調べた。BALB/c(H-2d)バックグラウンドの分泌型IL-15TgマウスにL. monocytogenesを感染させて7日目に脾臓で産生されるListeria抗原特異的メモリー型CD8^+T細胞をFITCで蛍光ラベルしたLLO(リステリオリシン)ペプチド+H-2Kd4量体で染色して、ソーテングした。この時期のLLO_<91-99>特異的CD8T細胞はIL-15Tgマウス、コントロールマウスともにCCR7の発現を認めないエフェクタータイプであったが、IL15TgマウスCD8T細胞はBcl-2の発現がコントロールマウスに比べて有意に高まっていた。コントロールマウスの感染7日目のLLO_<91-99>特異的CD8T細胞をCFSEで蛍光ラベルして、ナイーブIL-15Tgマウスまたはコントロールマウスに移入し、6週間後での細胞分裂をフローサイトメーターで調べたところ、IL-15Tgマウスへ移入した群で有意に高い細胞分裂を示した。IL-15の過剰発現はエフェクターCD8T細胞のactivation-induced apoptosisを防ぎ、さらに細胞分裂を誘導することによって、メモリーCD8T細胞数を増加させたと考えられる。一方、内因性IL-15の産生が抑制されている非分泌型IL-15Tgマウスでは感染後のIL-15の産生は認められず、感染7日目のLLO_<91-99>特異的CD8T細胞数はコントロールマウスに有意に低下していた。IL-15はエフェクターCD8T細胞の産生にも関与していると考えられる。

Research Products

(11 results)

All Other

All Publications (11 results)

[Publications] Ishimitsu, R.: "Overexpression of Interleukin-15 in vivo enhances Tcl response which inhibits allergic inflammation in a murine model of asthma"J. Immunol.. 166. 1991-2001 (2001)
[Publications] Nishimura, H.: "Mice lacking IL-2/IL-15 receptor β chain are susceptible but mice lacking IL-2 are resistant to infection with avirulent Salmonella choleraesuis"Infect. Immun.. 69. 1226-1229 (2001)
[Publications] Yajima, T.: "Memory phenotype CD8+T cells increased in IL-15 transgenic mice are involved in early protection against a primary infection with Listeria monocytogenes"Eur. J. Immunol.. 31. 757-766 (2001)
[Publications] Umemura, M.: "Impaired IL-15 production in murine AIDS mice might uderlie susceptibility to mycobacterial infection"J. Leuko. Biol.. 69. 138-148 (2001)
[Publications] Umemura, M.: "Overexpression of IL-15 in vivo induces a predominant Tcl response in mice inoculated with Mycobacterium bovis Bacille Calmette-Guerin infection"J. Immunol.. 167. 946-956 (2001)
[Publications] Masuda, A.: "Interleukin-15 prevents mouse mast cells from apoptosis through STAT6-mediated Bcl-xL Expression"J. Biol. Chem.. 276. 26107-26113 (2001)
[Publications] Yoshikai Y: "The role of prostaglandins and leukotoriens in acute inflammation caused by bacterial infection"Curr. Opin. Infect. Disease. 14. 257-264 (2001)
[Publications] Matsuguchi, T.: "A novel MAP kinase phosphatase is an important negative regulator of LPS-mediated JNK activation in mouse macrophage cell lines"Mol. Cell. Biol.. 20. 6999-7009 (2001)
[Publications] Yajima, T.: "Overexpression of IL-15 in vivo Increases antigen-driven memory CD8^+T cells following a microbe exposure"J. Immunol.. 168. 1198-1203 (2002)
[Publications] Shimizu, H.: "Toll-like receptor 2 contributes to liver injury induced by Salmonella infection through Fas ligand expression on NKT cells in mice"Gastroenterology. (in press). (2002)
[Publications] Yajima, T.: "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"Int. J. Cancer.. (in press). (2002)

2001 Fiscal Year Annual Research Report

インターロイキン15によるメモリー型CD8^+T細胞のシグナル伝達機構

Principal Investigator

吉開 泰信 名古屋大学, 大学院・医学研究科, 教授 (90158402)

Research Products

[Publications] Ishimitsu, R.: "Overexpression of Interleukin-15 in vivo enhances Tcl response which inhibits allergic inflammation in a murine model of asthma"J. Immunol.. 166. 1991-2001 (2001)

[Publications] Nishimura, H.: "Mice lacking IL-2/IL-15 receptor β chain are susceptible but mice lacking IL-2 are resistant to infection with avirulent Salmonella choleraesuis"Infect. Immun.. 69. 1226-1229 (2001)

[Publications] Yajima, T.: "Memory phenotype CD8+T cells increased in IL-15 transgenic mice are involved in early protection against a primary infection with Listeria monocytogenes"Eur. J. Immunol.. 31. 757-766 (2001)

[Publications] Umemura, M.: "Impaired IL-15 production in murine AIDS mice might uderlie susceptibility to mycobacterial infection"J. Leuko. Biol.. 69. 138-148 (2001)

[Publications] Umemura, M.: "Overexpression of IL-15 in vivo induces a predominant Tcl response in mice inoculated with Mycobacterium bovis Bacille Calmette-Guerin infection"J. Immunol.. 167. 946-956 (2001)

[Publications] Masuda, A.: "Interleukin-15 prevents mouse mast cells from apoptosis through STAT6-mediated Bcl-xL Expression"J. Biol. Chem.. 276. 26107-26113 (2001)

[Publications] Yoshikai Y: "The role of prostaglandins and leukotoriens in acute inflammation caused by bacterial infection"Curr. Opin. Infect. Disease. 14. 257-264 (2001)

[Publications] Matsuguchi, T.: "A novel MAP kinase phosphatase is an important negative regulator of LPS-mediated JNK activation in mouse macrophage cell lines"Mol. Cell. Biol.. 20. 6999-7009 (2001)

[Publications] Yajima, T.: "Overexpression of IL-15 in vivo Increases antigen-driven memory CD8^+T cells following a microbe exposure"J. Immunol.. 168. 1198-1203 (2002)

[Publications] Shimizu, H.: "Toll-like receptor 2 contributes to liver injury induced by Salmonella infection through Fas ligand expression on NKT cells in mice"Gastroenterology. (in press). (2002)

[Publications] Yajima, T.: "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"Int. J. Cancer.. (in press). (2002)

吉開泰信名古屋大学, 大学院・医学研究科, 教授 (90158402)