1998 Fiscal Year Annual Research Report

AIDS及びマウスAIDSモデルにおける複合感染症の病態解明とその治療法の開発

Research Project

Project/Area Number	10045068
Research Category	Grant-in-Aid for international Scientific Research
Section	University-to-University Cooperative Research
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)	WORAWIDH Waj カセサート大学, 獣医学部, 助教授西村仁志名古屋大学, 医学部, 助手 (00283440)
Keywords	MAIDS / マイコバクテリア / 複合感染 / IL-15 / NK細胞 / Th1細胞
Research Abstract	後天性免疫不全症候群(AIDS)患者の細菌(結核菌、サルモネラ菌)や真菌(ニューモシスティスカリニ)、原注(ルーシュマニア、トキソプラズマ)、ウイルス(サイトメカロウイルス)などの日和見複合感染症の病態の究明と治療法の確立が急がれている。我々は、カセサート大学と共同でマウスレトロウイルス感染症モデルの開発とその病態形成の分子機序を解析している。現在までにマウス白血病ウイルス(LP-BM5)感染によるMAIDS発症マウスを用いて、そのBCG複合感染症モデルを作成した。 MAIDS発症マウスでは、BCGに対する抵抗性が低下しており、死亡率の増加、菌排除能の低下が認められた。感染早期のマクロファージのIL-15 mRNAの発現、IL-15蛋白の産生能がMAIDSマウスでは著しく低下しており、その時期に一致してナチュラルキラー細胞、γδT細胞、更に血中の什N-γ(ガンマインターフェロン)の出現が低下していた。感染28日目のPPD特異的T細胞のIFN-γの産生は、MAIDSで著しく低下していた。これらの結果よりMAIDSではIL-15産生低下に伴って、感染早期防御機構が低下し、さらにTh1細胞産生が悪いために、BCGに対する感染防御が低下していると考えられる。

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] Tanano,M.: "Dibutyryl cyclic adenosine monophosphate protects mice against tumor necrosis factor-α-indu〓 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^- CD8αα^+ 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 Vα14^+NK1.1^+ T cells for liver injury induced by Salmonella infection." Hepatology.(in press.). (1999)
[Publications] Ishigami,M.: "The roles of intrahepatic γδ-T cells 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 strain 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

AIDS及びマウスAIDSモデルにおける複合感染症の病態解明とその治療法の開発

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] Tanano,M.: "Dibutyryl cyclic adenosine monophosphate protects mice against tumor necrosis factor-α-indu〓 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^- CD8αα^+ 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 Vα14^+NK1.1^+ T cells for liver injury induced by Salmonella infection." Hepatology.(in press.). (1999)

[Publications] Ishigami,M.: "The roles of intrahepatic γδ-T cells 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 strain 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)