2003 Fiscal Year Annual Research Report

細菌感染で誘導されるメモリーCD8+T細胞の産生/維持機構とその役割

Research Project

Project/Area Number	13226036
Research Institution	Kyushu University
Principal Investigator	吉開泰信九州大学, 生体防御医学研究所, 教授 (90158402)
Keywords	IL-15 / メモリーCD8T細胞 / 細胞傷害活性 / 肝傷害 / IL-15トランスジェニックマウス / IL-15ノックアウトマウス / Listeria monocytogene / BCG
Research Abstract	(1)IL-15トランスジェニック(Tg)マウスとIL-15ノックアウト(KO)マウスを用いて、卵白アルブミン(OVA)産生Listeria monocytogene(rOVALm)感染後のMHCクラスIb(H-2M-3)拘束性およびMHCクラスIa(H-2Kb)拘束性メモリーCD8T細胞をテトラーマー染色、サイトカインFACSおよびin vivo killer活性で比較した。感染5日目のMHC抗原特異的CD8T細胞数は各群で差を認めなかったが、キラー活性はIL-15Tgマウスで有意に高く、IL-15KOマウスで低かった。感染60日目では抗原特異的メモリーCD8T細胞数はIL-15Tgマウスでおおく、IL-15KOマウスで少なかった。OT-1TgマウスからOVA特異的CD8T細胞を正常マウスに移入してrOVALmを感染させてメモリーT細胞としてさらにIL-15TgマウスとIL-15KOマウスに移入してrOVALmに対する二次応答をみたところ、キラー活性はIL-15Tgマウスで有意にたかく、IL-15KOマウスで低かった。以上の結果からIL-15はメモリ-CD8T細胞に維持のみならず、キラー活性に重要であることが明らかとなった。 (2)IL-15TgマウスとIL-15KOマウスにMycobacterium bovis(BCG)を感染させて7日後にLPSを投与して肝障害の程度を比較した。肝障害はIL-15Tgマウスで有意に高く、IL-15KOマウスで低かった。抗CD8抗体または抗IFN-γ抗体でコントロールマウスおよびIL-15Tgマウスでの肝障害が著明に軽減されたことから、CD8Tc1細胞が肝障害のエフェクター細胞であることがわかった。BCG感染IL-15Tgマウスの肝臓リンパ球をLPSでin vitroで培養するとIFN-γ陽性CD8Tc1細胞が増加し、抗IL-12抗体でその増加が阻害された。以上の結果よりIL-15で活性化された肝臓のCD8T細胞が肝障害に重要な役割を担っていることが明らかになった。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] Ishimitsu, R.et al.: "NKT cells are dispensable in induction of oral tolerance but indispensable in abrogation of oral tolerance by prostaglandin E."Eur.J.Immunol. 33. 183-193 (2003)
[Publications] Musikacharoen, T.et al.: "Histone acetylation and activation of CREB regulate transcriptional activation of MKP-M in LPS-stimulated macrophages."J Biol Chem.. 278. 9167-9175 (2003)
[Publications] Hiromatsu, T.et al.: "Overexpression of IL-15 protects against Escherichia coli-induced shock accompanied by inhibition of TNF-α-induced apoptosis"J.Infect.Dis.. 187. 1442-1451 (2003)
[Publications] Matsuguchi, T.et al.: "JNK-interacting protein 3 associates with Toll-like receptor 4 and is involved in LPS-mediated JNK activation"EMBO J.. 22. 4455-4464 (2003)
[Publications] Hiromatsu, T.et al.: "NK T cells stimulated with a ligand for TLR2 contribute to liver injury caused by Escherichia coli infection in mice."Eur.J.Immunol.. 33. 2511-2519 (2003)
[Publications] Saito, K.et al.: "Soluble branched (1,4)-β-D-glucans from Acetobacter species show strong activities to induce IL-12 in vitro and inhibit Th2 response with IgE production in vivo."J Biol Chem.. 278. 38571-38578 (2003)
[Publications] Umemura, M.et al.: "Interleukin-15 as an immune adjuvant to increase efficacy of Bacillus Calmette-Guerin vaccination"Infect.Immun.. 71. 6045-6048 (2003)
[Publications] Kikuchi, T.et al.: "Cot/Tpl2 is essential for RANKL induction by lipid A in osteoblasts"J.Dent.Res.. 82. 542-545 (2003)
[Publications] Matsuguchi, T.et al.: "Lipoteichoic acids from Lactobacillus strains elicit strong tumor necrosis factor alpha-inducing activities, in macrophages through Toll-like receptor 2"Clin.Diagn.Lab.Immunol.. 10. 259-266 (2003)
[Publications] Abe, T.et al.: "Predominant IL-10 production by Kupffer cells is responsible for impaired bacterial clearance in mice with obstructive cholestasis"Hepatology. In press. (2004)
[Publications] Yajima, T.et al.: "Overexpression of IL-15 increases susceptibility to lethal endotoxic shock in mice primed with Mycobacterium bovis BCG"Infect.Immun.. In press. (2004)
[Publications] Nishimura, H.et al.: "Intraepithelilal γδ T cells may bridge a gap between innate and acquired immunity to herpes simplex virus type 2"J.Virol. In press. (2004)
[Publications] 吉開泰信: "ウイルス・細菌と感染症がわかる"羊土社. 133 (2003)

2003 Fiscal Year Annual Research Report

細菌感染で誘導されるメモリーCD8+T細胞の産生/維持機構とその役割

Principal Investigator

吉開 泰信 九州大学, 生体防御医学研究所, 教授 (90158402)

Research Products

[Publications] Ishimitsu, R.et al.: "NKT cells are dispensable in induction of oral tolerance but indispensable in abrogation of oral tolerance by prostaglandin E."Eur.J.Immunol. 33. 183-193 (2003)

[Publications] Musikacharoen, T.et al.: "Histone acetylation and activation of CREB regulate transcriptional activation of MKP-M in LPS-stimulated macrophages."J Biol Chem.. 278. 9167-9175 (2003)

[Publications] Hiromatsu, T.et al.: "Overexpression of IL-15 protects against Escherichia coli-induced shock accompanied by inhibition of TNF-α-induced apoptosis"J.Infect.Dis.. 187. 1442-1451 (2003)

[Publications] Matsuguchi, T.et al.: "JNK-interacting protein 3 associates with Toll-like receptor 4 and is involved in LPS-mediated JNK activation"EMBO J.. 22. 4455-4464 (2003)

[Publications] Hiromatsu, T.et al.: "NK T cells stimulated with a ligand for TLR2 contribute to liver injury caused by Escherichia coli infection in mice."Eur.J.Immunol.. 33. 2511-2519 (2003)

[Publications] Saito, K.et al.: "Soluble branched (1,4)-β-D-glucans from Acetobacter species show strong activities to induce IL-12 in vitro and inhibit Th2 response with IgE production in vivo."J Biol Chem.. 278. 38571-38578 (2003)

[Publications] Umemura, M.et al.: "Interleukin-15 as an immune adjuvant to increase efficacy of Bacillus Calmette-Guerin vaccination"Infect.Immun.. 71. 6045-6048 (2003)

[Publications] Kikuchi, T.et al.: "Cot/Tpl2 is essential for RANKL induction by lipid A in osteoblasts"J.Dent.Res.. 82. 542-545 (2003)

[Publications] Matsuguchi, T.et al.: "Lipoteichoic acids from Lactobacillus strains elicit strong tumor necrosis factor alpha-inducing activities, in macrophages through Toll-like receptor 2"Clin.Diagn.Lab.Immunol.. 10. 259-266 (2003)

[Publications] Abe, T.et al.: "Predominant IL-10 production by Kupffer cells is responsible for impaired bacterial clearance in mice with obstructive cholestasis"Hepatology. In press. (2004)

[Publications] Yajima, T.et al.: "Overexpression of IL-15 increases susceptibility to lethal endotoxic shock in mice primed with Mycobacterium bovis BCG"Infect.Immun.. In press. (2004)

[Publications] Nishimura, H.et al.: "Intraepithelilal γδ T cells may bridge a gap between innate and acquired immunity to herpes simplex virus type 2"J.Virol. In press. (2004)

[Publications] 吉開泰信: "ウイルス・細菌と感染症がわかる"羊土社. 133 (2003)

吉開泰信九州大学, 生体防御医学研究所, 教授 (90158402)