1998 Fiscal Year Annual Research Report

IL-15による新しい癌免疫療法の開発のための基礎的研究

Research Project

Project/Area Number	10153222
Research Institution	Nagoya University
Principal Investigator	吉開泰信名古屋大学, 医学部, 教授 (90158402)
Keywords	IL-15 / 癌性胸膜炎 / NK細胞 / CD8細胞 / ガンマインターフェロン / 感染
Research Abstract	IL-15の腫瘍や感染症での防御機構における役割を明らかにするために、マウスの癌性胸膜炎モデル、大腸菌感染症、サルモネラ感染症、さらに単純ヘルペス2型(HSV-2)感染症モデルにおけるIL-15の役割を検討した。 IL-15の抗腫瘍効果を、Meth A胸腔内接種BALB/cマウスモデルを用いて、レコンビナントIL-15を投与する系で検討した。IL-15 100ngを腫瘍接種後3回投与した群では、コントロール群に比べて有意に生存率を高めた。胸腔内浸出細胞を用いたWinn assayでは、胸腔内浸出細胞からasialo GM1陽性細胞またはCD8陽性細胞を除去することによって抗腫瘍効果が減少した。このことからIL-15による抗腫瘍効果は、asialo GMl陽性のNK細胞とCD8T細胞がエフェクター細胞として働いていることが明らかとなった。 HSV-2型感染症モデルにおいてIL-15 500ngを腹腔感染後、5日間連日投与すると、NK細胞、CD8T細胞の増加とHSV-2特異的CD4Thl細胞の活性化が認められ、強い抵抗性を賦与することができた。マウスの大腸菌感染症(E.coli.ATCC26)及びサルモネラ感染症(Salmonella choleraesuis,31N-1)での内因性IL-15の役割を明らかにするために、抗IL-15抗体投与マウスを用いて検討した。その結果、大腸菌感染症では、γδ型T細胞の増加が、サルモネラ感染症ではNK細胞の増加が、それぞれ阻害され、感染抵抗性が減弱した。

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^- 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 translaation 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

IL-15による新しい癌免疫療法の開発のための基礎的研究

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^- 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 translaation 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)