2000 Fiscal Year Annual Research Report

CD8^+T細胞による免疫記憶形成でのインターロイキン15の役割

Research Project

Project/Area Number	12051217
Research Institution	Nagoya University
Principal Investigator	吉開泰信名古屋大学, 医学部, 教授 (90158402)
Keywords	IL-15 / トランスジェニックマウス / メモリーCD8T細胞 / Listeria monocytogenes / BCG / LLO_<91-99> / H-2K^d
Research Abstract	分泌型IL-15cDNAをMHCクラスIプロモーターをもつ発現ベクターに組み込み、トランスジェニック(Tg)マウスを作製した。胸腺でのT細胞分化は正常マウスとかわらなかったが、血清中のIL-15レベルが高まっており、脾臓、リンパ節でのメモリー型CD8T細胞が有意に増加していた。このIL-15Tgマウスに致死量以下のListeria monocytogenesを静脈内に感染させた。K-2K^dと結合するListeria抗原エピトープであるLLO_<91-99>をH-2K^dの四量体を結合させ、さらに蛍光ラベルして、CD8^+T細胞の中でのLLO_<91-99>/H-2K^d四量体に結合する割合を感染経時的に比較検討した。感染7日目ではTgマウスではコントロール群とLLO_<91-99>陽性CD8T細胞数に差を認めなかったが、感染21日目以降ではメモリー型(CD44^+CD8^+Ly6c^+)LLO_<91-99>/H-2K^d陽性CD8T細胞がIL-15Tgマウスで有意に増加していた。このLLO_<91-99>/H-2K^d陽性CD8T細胞をセルソーターで分離してその遺伝子発現を調べたところ、anti-apoptotic proteinであるBCL2,BclXLの発現が高かった。次にIL-15TgマウスにMycobacterium bovis BCGを感染させたところ、強い感染抵抗性を示した。BCG感染IL-15TgマウスではNK細胞数の増加とPPD特異的CD8T細胞の産生の増加が認められた。抗CD8抗体のin vivo投与によって菌数が増加した。これらの結果より、IL-15はメモリーCD8T細胞の維持に働き、感染防御を増強すると考えられる。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Nishimura,H.: "Differential roles of IL-15 mRNA isoforms generated by alternative splicing in immune responses in vivo."J.Exp.Med.. 191. 157-170 (2000)
[Publications] Kimura,K.: "Synergistic effect of IL-15 and IL-12 on anti-tumor activity in a murine malignant pleurisy model."Cancer.Immunol.Immunother.. 49. 71-77 (2000)
[Publications] Yoshikai,Y.: "The role of interleukin 15 in mounting an immune response against microbial infections."Microbes.Infect.. 2. 381-389 (2000)
[Publications] Mokuno,Y.: "Expression of Toll-like receptor 2 on γδT cells bearing invariant Vγ6/Vδ1 indyced by Escherichia coli infection."J.Immunol.. 165. 931-940 (2000)
[Publications] Murosaki,S.: "Antitumor effect of heat-killed Lactobacillus plantarum L-137 throuigh restoration of impaired IL-12 production in tumor-bearing mice."Cancer.Immunol.Immunother.. 49. 157-164 (2000)
[Publications] Masuda,A.: "Interleukin-15 induces rapid tyrosine phosphorylation of STAT6 and the expression of interleukin-4 in mouse mast cells."J.Biol.Chem.. 275. 29331-29337 (2000)
[Publications] Matsuguchi,T.: "Gene expression of Toll-like receptor 2 but not Toll-like receptor 4, is induced by LPS and inflammatory cytokines in mouse macrophages."J.Immunol. 165. 5767-5772 (2000)
[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] 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 βchain 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.. (in press.). (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.. (in press.). (2001)

2000 Fiscal Year Annual Research Report

CD8^+T細胞による免疫記憶形成でのインターロイキン15の役割

Principal Investigator

吉開 泰信 名古屋大学, 医学部, 教授 (90158402)

Research Products

[Publications] Nishimura,H.: "Differential roles of IL-15 mRNA isoforms generated by alternative splicing in immune responses in vivo."J.Exp.Med.. 191. 157-170 (2000)

[Publications] Kimura,K.: "Synergistic effect of IL-15 and IL-12 on anti-tumor activity in a murine malignant pleurisy model."Cancer.Immunol.Immunother.. 49. 71-77 (2000)

[Publications] Yoshikai,Y.: "The role of interleukin 15 in mounting an immune response against microbial infections."Microbes.Infect.. 2. 381-389 (2000)

[Publications] Mokuno,Y.: "Expression of Toll-like receptor 2 on γδT cells bearing invariant Vγ6/Vδ1 indyced by Escherichia coli infection."J.Immunol.. 165. 931-940 (2000)

[Publications] Murosaki,S.: "Antitumor effect of heat-killed Lactobacillus plantarum L-137 throuigh restoration of impaired IL-12 production in tumor-bearing mice."Cancer.Immunol.Immunother.. 49. 157-164 (2000)

[Publications] Masuda,A.: "Interleukin-15 induces rapid tyrosine phosphorylation of STAT6 and the expression of interleukin-4 in mouse mast cells."J.Biol.Chem.. 275. 29331-29337 (2000)

[Publications] Matsuguchi,T.: "Gene expression of Toll-like receptor 2 but not Toll-like receptor 4, is induced by LPS and inflammatory cytokines in mouse macrophages."J.Immunol. 165. 5767-5772 (2000)

[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] 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 βchain 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.. (in press.). (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.. (in press.). (2001)

吉開泰信名古屋大学, 医学部, 教授 (90158402)