1999 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体解明とその治療法の開発

Research Project

Project/Area Number	10045068
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	MAIDS / マイコバクテリア / 複合感染 / NK細胞 / Th1細胞 / IL-15トランスジェニックマウス / メモリーCD8T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)、原虫(ルーシュマニア、トキソプラズマ)、ウイルス(サイトメガロウイルス)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、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ことを見いだした。さらにIL-15のMAIDSそのものの進展における役割を明らかにするために、分泌型IL-15cDNAを用いてトランスジェニック(Tg)マウスを作製した。IL-15Tgマウスの胸腺でのT細胞分化は正常マウスと変わらなかったが、脾臓、リンパ節でのメモリ型CD8^+T細胞が有意に増加していた。このIL-15Tgマウスを用いて、LP-BM5マウス白血病ウイルスの感染によって引き起こされるMAIDSの発症程度を生存率、脾腫、異常リンパ球(Thy1陰性、Fas陽性、IgM^<dull>細胞など)の出現頻度、LP-BM5 viral DNAのintegration量で比較したところ、MAIDSの発症がIL-15Tgマウスで有意に抑制された。IL-15産生不全がMAIDSの病態形成に関与していると考えられる。

Research Products
(22 results)

All Other

All Publications (22 results)

[Publications] Kimura,K.: "Immunogene therapy for murine fibrosarcoma using IL-15 gene with high translation efficiency."Eur.J.Immunol.. 29. 1532-1542 (1999)
[Publications] Hirose,K.: "Endogenous IL-15 might be responsible for early protection by natural killer cells against infection with an avirulent strain of Salmonella choleraesuis in mice."J.Leukocyte Biol.. 66. 382-390 (1999)
[Publications] Mayumi,T.: "IL-15 is elevated in the patients of postoperative enterocolitis."Cytokine. 11. 888-893 (1999)
[Publications] Mitani,A.: "Interleukin-15 might be responsible for early activation of intestinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in mice."Immunology. 97. 92-99 (1999)
[Publications] Yamada,K.: "Characterization of CD4^+ CD8αα^+ and CD4^- CD8αα^+ intestinal intraepithelial lymphocytes in rats."Int.Immunol.. 11. 21-28 (1999)
[Publications] Nishimura,H.: "MHC class II-dependent NK1.1^+ γδT cells are induced in mice by Salmonella infection."J.Immunol.. 162. 1573-1581 (1999)
[Publications] Ishigami,M.: "The roles of intrahepatic Vα14^+NK1.1^+T cells for liver injury induced by Salmonella infection."Hepatology.. 29. 1799-1808 (1999)
[Publications] Naiki,Y.: "Regulatory role of peritoneal NK1.1^+αβ T cells in IL-12 production during Salmonella infection."J.Immunol.. 163. 2057-2063 (1999)
[Publications] Tanaka,S.: "Activation of T cells recognizing an epitope of heat shock protein (HSP)70 can protect against rat adjuvant arthritis."J.Immunol.. 163. 5560-5565 (1999)
[Publications] Mokuno,Y.: "Prostaglandin E_1 protects against liver injury induced by Escherichia coli infection via a dominant Th2-like response of liver T Cells in mice."Hepatology.. 30. 1464-1472 (1999)
[Publications] Nishimura,H.: "Differencial roles of IL-15 mRNA isoforms generated by alternative splicing in immune responses in vivo."J.Exp.Med.. 191. 157-170 (2000)
[Publications] Matsuguchi,T.: "Gene expressions of lipopolysaccharide receptors,Toll-like receptors 2 and 4,are differently regulated in mouse T lymphocytes."Blood.. 95. 1378-1385 (2000)
[Publications] Kimura,K.: "Synergistic effect of IL-15 and IL-12 on anti-tumor activity in a murine malignant pleurisy model."Cancer.Immuno.Immunother.. (in press). (2000)
[Publications] Mokuno,Y.: "γδ T cells bearing invariant Vγ6/Vδ1 may respond to lipid A via Toll-like receptor 2."J.Immunol.. (in press). (2000)
[Publications] Murosaki,S.: "Antitumor effect of heat-killed Lactobacillus plantarum L-137 through restoration of impaired IL-12 production in tumor-bearing mice."Cancer.Immuno.Immunother.. (in press). (2000)
[Publications] 吉開泰信: "初期感染防御におけるサイトカインの役割"Molecular Medicine. 36. 528-537 (1999)
[Publications] 吉開泰信: "TCRを介さないLPSによるγδ細胞の活性化"臨床免疫. 31. 727-733 (1999)
[Publications] 松口徹也: "感染症における免疫担当細胞としてのγδT細胞の役割とサイトカイン"Surgery Frontier. 6. 29-37 (1999)
[Publications] 吉開泰信: "TCR"遺伝子医学. 3巻・1号. 63-68 (1999)
[Publications] 西村仁志: "Annual Review免疫"The γδT-cell bridge. 41-47 (1998)
[Publications] 吉開泰信: "内科学II"微生物の病原性とヒトの生体防御機構. 1838-1844 (1999)
[Publications] 吉開泰信: "免疫と血液の科学"サイトカインによる免疫制御. 107-130 (1999)

1999 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体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] Kimura,K.: "Immunogene therapy for murine fibrosarcoma using IL-15 gene with high translation efficiency."Eur.J.Immunol.. 29. 1532-1542 (1999)

[Publications] Hirose,K.: "Endogenous IL-15 might be responsible for early protection by natural killer cells against infection with an avirulent strain of Salmonella choleraesuis in mice."J.Leukocyte Biol.. 66. 382-390 (1999)

[Publications] Mayumi,T.: "IL-15 is elevated in the patients of postoperative enterocolitis."Cytokine. 11. 888-893 (1999)

[Publications] Mitani,A.: "Interleukin-15 might be responsible for early activation of intestinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in mice."Immunology. 97. 92-99 (1999)

[Publications] Yamada,K.: "Characterization of CD4^+ CD8αα^+ and CD4^- CD8αα^+ intestinal intraepithelial lymphocytes in rats."Int.Immunol.. 11. 21-28 (1999)

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

[Publications] Ishigami,M.: "The roles of intrahepatic Vα14^+NK1.1^+T cells for liver injury induced by Salmonella infection."Hepatology.. 29. 1799-1808 (1999)

[Publications] Naiki,Y.: "Regulatory role of peritoneal NK1.1^+αβ T cells in IL-12 production during Salmonella infection."J.Immunol.. 163. 2057-2063 (1999)

[Publications] Tanaka,S.: "Activation of T cells recognizing an epitope of heat shock protein (HSP)70 can protect against rat adjuvant arthritis."J.Immunol.. 163. 5560-5565 (1999)

[Publications] Mokuno,Y.: "Prostaglandin E_1 protects against liver injury induced by Escherichia coli infection via a dominant Th2-like response of liver T Cells in mice."Hepatology.. 30. 1464-1472 (1999)

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

[Publications] Matsuguchi,T.: "Gene expressions of lipopolysaccharide receptors,Toll-like receptors 2 and 4,are differently regulated in mouse T lymphocytes."Blood.. 95. 1378-1385 (2000)

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

[Publications] Mokuno,Y.: "γδ T cells bearing invariant Vγ6/Vδ1 may respond to lipid A via Toll-like receptor 2."J.Immunol.. (in press). (2000)

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

[Publications] 吉開泰信: "初期感染防御におけるサイトカインの役割"Molecular Medicine. 36. 528-537 (1999)

[Publications] 吉開泰信: "TCRを介さないLPSによるγδ細胞の活性化"臨床免疫. 31. 727-733 (1999)

[Publications] 松口徹也: "感染症における免疫担当細胞としてのγδT細胞の役割とサイトカイン"Surgery Frontier. 6. 29-37 (1999)

[Publications] 吉開泰信: "TCR"遺伝子医学. 3巻・1号. 63-68 (1999)

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

[Publications] 吉開泰信: "内科学II"微生物の病原性とヒトの生体防御機構. 1838-1844 (1999)

[Publications] 吉開泰信: "免疫と血液の科学"サイトカインによる免疫制御. 107-130 (1999)

吉開泰信名古屋大学, 医学部, 教授 (90158402)