2001 Fiscal Year Annual Research Report

細菌感染で誘導されるメモリーCD8細胞の産生/維持機構とその役割

Research Project

Project/Area Number	13226036
Research Category	Grant-in-Aid for Scientific Research on Priority Areas (C)
Research Institution	Nagoya University
Principal Investigator	吉開泰信名古屋大学, 医学研究科, 教授 (90158402)
Keywords	IL-15 / L.monocytogenes / トランスジェニックマウス / メモリーCD8T細胞 / Bcl-2 / 細胞分裂
Research Abstract	細胞内寄生性細菌に対して細胞傷害活性やγインターフェロン(γIFN)産生能をもつCD8T細胞は重要な防御機構を担う。一方、インターロイキン(IL)-15のメモリーCD8^+T細胞の活性化と維持に働く。本年度は正常マウスとIL-15トランスジェニツク(Tg)マウス(H-2d背景)に細胞内寄生性細菌Listeria monocytogenesを感染させて脾臓に産生するメモリー型CD8T細胞をリステリオリシン(LLO)由来の91-99ペプチドを結合させたFITCラベルH-2Kd4量体を用いて、フローサイトメターにて経時的に観察した。感染7日目では正常マウスに比べて、IL-15Tgマウスの脾臓でLLO_<91-99>特異的CD8T細胞は相対的に少なく、この時期では抗原非特異的なCD8T細胞がポリクローナルに増加しているためと考えられた。一方、菌が完全に排除された感染21日以降では、LLO_<91-99>特異的CD8T細胞はIL-15Tgマウスの脾臓で有意に増加していた。セルソーターで分離したLLO_<91-99>特異的CD8T細胞は7日目ではCCR7の発現を認めないエフェクタータイプであったが、感染21日以降のLLO特異的CD8T細胞はCCR7を発現するセントラルメモリー型であった。このメモリー型CD8T細胞はBcl-2の発現が高まっていた。感染7日目の脾臓由来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マウスまたはに移入し、6週間後に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。これらの結果から、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。

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

細菌感染で誘導されるメモリーCD8細胞の産生/維持機構とその役割

Principal Investigator

吉開 泰信 名古屋大学, 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] Yoshikai Y: "The role of prostaglandins and leukotoriens in acute inflammation caused by bacterial infection"Curr.Opin.Infect.Disease. 14. 257-264 (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] 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, 医学研究科, 教授 (90158402)