1998 Fiscal Year Annual Research Report

遺伝子ノックアウトマウスを用いた細菌初期防御機構の分子基盤の解析

Research Project

Project/Area Number	09470076
Research Institution	Nagoya University
Principal Investigator	吉開泰信名古屋大学, 医学部, 教授 (90158402)
Co-Investigator(Kenkyū-buntansha)	西村仁志名古屋大学, 医学部, 助手 (00283440)
Keywords	γδ型T細胞 / 大腸菌 / LPS / IL-15 / ノックアウトマウス
Research Abstract	γδ型T細胞は、個体の発生早期に出現し、表皮や腸管などの上皮間に多く存在するユニークなTリンパ球である。その機能としては感染の初期防御機構として、上皮系では上皮の分化促進や粘膜免疫制御機構として働くことが報告されている。我々はγδ型T細胞の抗原認識とその機能を明らかにする目的でLPS反応性γδ型T細胞について解析した。 LPS高反応性C3H/HeN及びLPS低反応性C3H/HeJマウスにEscherichia coli(ATCC26)1x10^8CFUを腹腔内に投与して3日目の腹腔内滲出細胞のγδ型Tリンパ球の特性を比較した。 C3H/HeNでは、E.coli感染後γδ型T細胞の増加が認められたが、C3H/HeJではほとんど認められなかった。C3H/HeNで増加するγδ型T細胞は、N領域の多様性を認めないVγ6/Vδ1のinvariant chainを発現していた。このγδ型T細胞は抗TCRγδmAb-coated dishの上でLPSまたはLipid Aの存在下で抗原提示細胞なしで、増殖し、IFN-γを産生した。このγδ型T細胞はCD14の発現は認められず、またLPSレセプターのひとつと考えられるToll-like receptor 4(TLR-4)の発現も認められなかった。変異TLR-4を持つC3H/HeJマウスでのE.coli感染後のγδ型T細胞もLPSに反応してIFN-γを産生した。一方、腹腔マクロファージのIL-15の産生は、C3H/HeNで高く、C3H/HeJでは認められなかった。抗IL-15抗体で処理したC3H/HeNマウスではγδ型T細胞の増加は抑制され、感染抵抗性を減弱した。E.coli感染後のγδ型T細胞の出現にはIL-15が重要な役割を担うと考えられる。また、抗TCRγδmAb抗体処理マウスやTCRδノックアウトマウスでは菌の排除が遅れることより、γδ型T細胞が大腸菌の感染防御の役割を担うことがわかった。

Research Products

(22 results)

All Other

All Publications (22 results)

[Publications] Nishimura,H.: "Translational efficiency is upregulated by alternative exon in murine interleukin-15 mRNA." J.Immunol.160. 936-942 (1998)
[Publications] Kimura,Y.: "The regulatory role of heat shock protein 70-reactive CD4_+ T cells during rat listeriosis." Int.Immunol.10. 117-130 (1998)
[Publications] Sakai,T.: "Interleukin 15 activity in the intestinal mucosa of inflammatory bowel disease." Gastroenterology.114. 1237-1243 (1998)
[Publications] Washizu,J.: "NF-κB binding site is essential for transcriptional activation of IL-15." Immunogenetics. 48. 1-7 (1998)
[Publications] Takano,M.: "A protective role of IL-15-dependent γδ T cells in Escherichia coli infection in mice." Infect.Immun.66. 3270-3278 (1998)
[Publications] Takano,M.: "Dibutyryl cyclic adenosine monophosphate protects mice against tumor necrosis factor-α-induced hepatocyte apoptosis accompanied by increased heat shock protein 70 expression." Cell Stress & Chaperones.3. 109-117 (1998)
[Publications] Takano,M.: "Prostaglandin E2 protects against liver injury after Escherichia coli infection but hampers the resolution of the infection in mice." J.Immunol.161. 3019-3025 (1998)
[Publications] Hirose,K.: "Interleukin-15 might be responsible early activation of intestinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in rats." Infect.Immun.66. 5677-5683 (1998)
[Publications] Yamada,K.: "Characterization of CD4^+ CD8αα^+ and CD4^- CD8aa^+ intestinal intraepithelial lymphocytes in rats." Int.Immunol.11. 21-28 (1998)
[Publications] Nishimura,H.: "MHC class II-dependent NK1.1^+ γδ T cells are induced in mice by Salmonella infection." J.Immunol.162. 1573-1581 (1999)
[Publications] Mayumi,T.: "IL-15 is elevated in the patients of postoperative enterocllitis." Cytokine. (in press). (1999)
[Publications] Mitani,A.: "Interleukin-15 might be responsible for early activation of intestinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in mice." Immunolgy.(in press). (1999)
[Publications] Ishigami,M.: "The roles of intrahepatic Vα 14^+ NK1.1^+ T cells for liver injury induced by Salmonella infection." Hepatology.(in press). (1999)
[Publications] Ishigami,M.: "The roles of intrahepatic γδ-Tcells for liver injury in mouse induced by Salmonella infection." Microbiol.Immunol.(in press). (1999)
[Publications] Kimura,K.: "Immunogene therapy for murine fibrosarcoma using IL-15 gene with high translation efficiency." Eur.J.Immunol.(in press). (1999)
[Publications] Hirose,K.: "Endogenous IL-15 might be responsible for early protection by natural killer cells against infection with avirulent atrain of Salmonella choleraesuis in mice." J.Leukocyte Biol.(in press). (1999)
[Publications] 吉開泰信: "感染制御とストレス蛋白質" 医学のあゆみ. 187. 241-246 (1998)
[Publications] 吉開泰信: "腸管における感染防御機構" INFECTION CONTROL. 7巻・9号. 32-37 (1998)
[Publications] 吉開泰信: "TCR" 遺伝子医学. 3巻・1号. 63-68 (1998)
[Publications] 西村仁志: "γδ型T細胞の新しいサブセット" 臨床医. 24巻・3号. 41-42 (1998)
[Publications] 西村仁志: "The γδ T-cell bridge" Annual Review免疫. 1999. 41-47 (1998)
[Publications] 西村仁志: "IL-15の生物活性と産生調節" Annual Review免疫. 1999. 119-125 (1998)

1998 Fiscal Year Annual Research Report

遺伝子ノックアウトマウスを用いた細菌初期防御機構の分子基盤の解析

Principal Investigator

吉開 泰信 名古屋大学, 医学部, 教授 (90158402)

Research Products

[Publications] Nishimura,H.: "Translational efficiency is upregulated by alternative exon in murine interleukin-15 mRNA." J.Immunol.160. 936-942 (1998)

[Publications] Kimura,Y.: "The regulatory role of heat shock protein 70-reactive CD4_+ T cells during rat listeriosis." Int.Immunol.10. 117-130 (1998)

[Publications] Sakai,T.: "Interleukin 15 activity in the intestinal mucosa of inflammatory bowel disease." Gastroenterology.114. 1237-1243 (1998)

[Publications] Washizu,J.: "NF-κB binding site is essential for transcriptional activation of IL-15." Immunogenetics. 48. 1-7 (1998)

[Publications] Takano,M.: "A protective role of IL-15-dependent γδ T cells in Escherichia coli infection in mice." Infect.Immun.66. 3270-3278 (1998)

[Publications] Takano,M.: "Dibutyryl cyclic adenosine monophosphate protects mice against tumor necrosis factor-α-induced hepatocyte apoptosis accompanied by increased heat shock protein 70 expression." Cell Stress & Chaperones.3. 109-117 (1998)

[Publications] Takano,M.: "Prostaglandin E2 protects against liver injury after Escherichia coli infection but hampers the resolution of the infection in mice." J.Immunol.161. 3019-3025 (1998)

[Publications] Hirose,K.: "Interleukin-15 might be responsible early activation of intestinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in rats." Infect.Immun.66. 5677-5683 (1998)

[Publications] Yamada,K.: "Characterization of CD4^+ CD8αα^+ and CD4^- CD8aa^+ intestinal intraepithelial lymphocytes in rats." Int.Immunol.11. 21-28 (1998)

[Publications] Nishimura,H.: "MHC class II-dependent NK1.1^+ γδ T cells are induced in mice by Salmonella infection." J.Immunol.162. 1573-1581 (1999)

[Publications] Mayumi,T.: "IL-15 is elevated in the patients of postoperative enterocllitis." Cytokine. (in press). (1999)

[Publications] Mitani,A.: "Interleukin-15 might be responsible for early activation of intestinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in mice." Immunolgy.(in press). (1999)

[Publications] Ishigami,M.: "The roles of intrahepatic Vα 14^+ NK1.1^+ T cells for liver injury induced by Salmonella infection." Hepatology.(in press). (1999)

[Publications] Ishigami,M.: "The roles of intrahepatic γδ-Tcells for liver injury in mouse induced by Salmonella infection." Microbiol.Immunol.(in press). (1999)

[Publications] Kimura,K.: "Immunogene therapy for murine fibrosarcoma using IL-15 gene with high translation efficiency." Eur.J.Immunol.(in press). (1999)

[Publications] Hirose,K.: "Endogenous IL-15 might be responsible for early protection by natural killer cells against infection with avirulent atrain of Salmonella choleraesuis in mice." J.Leukocyte Biol.(in press). (1999)

[Publications] 吉開泰信: "感染制御とストレス蛋白質" 医学のあゆみ. 187. 241-246 (1998)

[Publications] 吉開泰信: "腸管における感染防御機構" INFECTION CONTROL. 7巻・9号. 32-37 (1998)

[Publications] 吉開泰信: "TCR" 遺伝子医学. 3巻・1号. 63-68 (1998)

[Publications] 西村仁志: "γδ型T細胞の新しいサブセット" 臨床医. 24巻・3号. 41-42 (1998)

[Publications] 西村仁志: "The γδ T-cell bridge" Annual Review免疫. 1999. 41-47 (1998)

[Publications] 西村仁志: "IL-15の生物活性と産生調節" Annual Review免疫. 1999. 119-125 (1998)

吉開泰信名古屋大学, 医学部, 教授 (90158402)