1989 Fiscal Year Annual Research Report

エフェクター細胞の機能分化;サイトカインとそのレセプター系を中心としたアプローチ

Research Project

Project/Area Number	01010052
Research Institution	Kumamoto University
Principal Investigator	高津聖志熊本大学, 医学部, 教授 (10107055)
Co-Investigator(Kenkyū-buntansha)	吉永秀熊本大学, 医学部, 教授 (90040196) 平野俊夫大阪大学, 医学部, 教授 (40136718) 藤原大美大阪大学, 医学部, 助教授 (70116094) 菅村和夫東北大学, 医学部, 教授 (20117360) 熊谷勝男東北大学, 歯学部, 教授 (00005018)
Keywords	サイトカイン / サイトカインレセプター / エフェクター細胞 / 細胞傷害性T細胞 / ナチュラルキラー細胞 / T細胞抗原受容体 / 骨髄腫細胞 / B白血病細胞
Research Abstract	本研究は腫瘍免疫誘導ないし増強に関与するサイトカインおよびそれらの標的細胞上のレセプター系を中心にエフェクター細胞の機能分化を明らかにすることを研究目的としている。本年度は以下に示すような実績が得られた。(1)免疫アジュバントにより誘導される自己癌細傷害性細胞がTγ/δ陽性T細胞であることを示した。(2)ILー2レセプターβ鎖に対する単クローン抗体を作製するとともに、β鎖遺伝子を単離しその発現系を確立した。(3)殺細胞性機構において、細胞傷害性顆粒の蓄積と放出が不可欠であるが、NKやCTLにおいてはその放出機構が異なることを明らかにした。(4)腫瘍内にT細胞を浸潤させる機構として、先づ好中球がCD4^+T細胞の走化性因子を産生し、次いでCD4^+T細胞がCD8^+T細胞の走化性因子を産生することを明らかにし、その物質を精製した。(5)ILー6が多発性骨髄腫や腎細胞癌の自己増殖因子であることを明らかにするとともに、ILー6トランスジェニックマウスにおいては形質細胞の異常増殖がみられることを明らかにした。(6)慢性B白血病細胞を用いて、ILー5が高親和性ILー2レセプターの発現を増強させるのに、ILー4はそれ単独では無効であるのみならず、ILー5と共存するとILー5によるILー2レセプター発現増強効果を抑制することを示した。(7)炎症局所において、その早期にはILー1産生がみられるが後期にはILー1の産生がみられないことを示し、その理由としてILー1産生が終息した炎症後期に滲出する多核白血球がILー1インヒビターを産生することを見出した。(8)ILー5によるシグナル伝達は特異受容体を介し伝達されるがその過程は既知のキナーゼは関与しないが、リン酸化タンパクが関与していることを示し、ILー5受容体に対する単クローン抗体を作製した。(9)インターフェロンーγはCTLの産生を増強するが、B細胞の増殖を抑制し、TGFーβはIgA産生を選択的に増強することを示した。(10)T細胞不活性を調べる実験系を開発した。

Research Products

(22 results)

All Other

All Publications (22 results)

[Publications] Sonoda,E.,et al.: "Transforming growth factor induces IgA production and acts additively with interleukin 5 for IgA production." The Journal of Experimental Medicine. 170. 1415-1420 (1989)
[Publications] Hitoshi,Y.,et al.: "Interferon-gamma inhibits the proliferation but not the differentiation of murine B cells in response to IL-5." International Immunology. 1. 185-190 (1989)
[Publications] Takatsu,K.,et al.: "Signal transduction through interleukin-5 receptors." Cold Spring Harbor Synp.Quant.Biol.54. (1990)
[Publications] Sugamura,S.,et al.: "Analysis of mechanisms by which NK cells acquire increased cytotoxicity against class IMHC-eliminated targets." Cell.Immunol.119. 304-316 (1989)
[Publications] Fujii,M.,et al.: "Polyclonal activation of human lynphocytes streptococcal preparations.Evidence for interleukin2-independent generation“double negative(CD3 CD4 CD8 TcR16)"" J.Immunol.(1990)
[Publications] Shijubo,N.,et al.: "Functional analysis of mononuclear cells infiltration into tumors.A soluble factor involved in the regulation into tumors." J.Immunol.142. 2961-2967 (1989)
[Publications] Shijubo,N.,et al.: "Functional analysis of mononuclear cells infiltration into tumor-inflitration cells." Jpn.J.Cancer Res.81.
[Publications] Takeshita,T., et al.: "Monoclonal antibody defining a molecule possibly identical to the p75 submit of interleukin 2 receptor." The Journal of Experimental Medicine. 169. 1323-1332 (1989)
[Publications] Ohashi,Y.,et al.: "Differential expression of the interleukin 2 receptor subunits,p55 and p75 on various populations of primary peripheral blood mononuclear cells." The Journal of immunology. 143. 3548-3555 (1989)
[Publications] Sato,N.,et al.: "Anti-idiotype reactive with target molecule for mouse Lymphokine-activated killer cells." Cell.Immunol.121. 217-224 (1989)
[Publications] Nishimura,T.,et al.: "Inhibition of lymphokine-activated killer cell-mediated cytotoxicity by phorbol ester." The Journal of Immunology. 121. 2155-2161 (1989)
[Publications] Shimizu,J.,et al.: "Induction of tumor-specificin vivo protective immunization with tumor antigen-plused antigen-presenting cells." The Journal of immunology. 142. 1053-1059 (1989)
[Publications] Sano,S.,et al.: "Cytotoxic T lymphocyte unresponsiveness induced by prolonged treatment with immobilized anti-CD3:Association of impairment of cytolytic activity with temporary depletion of intracellular protein kinase." The Journal of immunology. 143. 2797-2805 (1989)
[Publications] Taga,T.,et al.: "Interleukin-6 triggers the association of its receptor with a possible signal transducer,gp130." Cell. 58. 573-581 (1989)
[Publications] Suematsu,S.,et al.: "IgG1 plasmacytosis in interleukin 6 transgenic mice." Proc.Nat1.Acad.Sci.USA.86. 7547-7551 (1989)
[Publications] Hirata,Y.,et al.: "Characterization of IL-6 receptor expression by monoclonal and polyclonal antibodies." The Journal of Immunology. 143. 2900-2906 (1989)
[Publications] Matsui,K.,et al.: "Us-and J-chain-mRNA expression are separately controlled event." The Journal of Immunology. 142. 2918-2923 (1989)
[Publications] Yoshimoto,T.,et al.: "IL-5 up-regulates but IL-4 down-regulates IL-2R expression on cloned B lymphoma line." The Journal of Immunology. 144. 183-190 (1990)
[Publications] Ohkawara,S.,et al.: "Interleukin 1 as an inflammatory hormon." Acta Pathol.Jap.39. 85-100 (1989)
[Publications] Goto,F.,et al.: "Biosynthesis of interleukin-1β at inflammatory site in rabbits.Kinetics and producing cells." Brit.J.Exp.Pathol.70. 597-606 (1989)
[Publications] Yamaguchi,N.,et al.: "Mechanisms of the interlekin 5-induced differentiation of B cells." J.Biochem.106. 837-843 (1989)
[Publications] Yamaguchi,N.,et al.: "Characterization of the murine interleukin 5 receptor by using a monoclonal antibody." Int.Immunol.2. 181-187 (1990)

1989 Fiscal Year Annual Research Report

エフェクター細胞の機能分化;サイトカインとそのレセプター系を中心としたアプローチ

Principal Investigator

高津 聖志 熊本大学, 医学部, 教授 (10107055)

Research Products

[Publications] Sonoda,E.,et al.: "Transforming growth factor induces IgA production and acts additively with interleukin 5 for IgA production." The Journal of Experimental Medicine. 170. 1415-1420 (1989)

[Publications] Hitoshi,Y.,et al.: "Interferon-gamma inhibits the proliferation but not the differentiation of murine B cells in response to IL-5." International Immunology. 1. 185-190 (1989)

[Publications] Takatsu,K.,et al.: "Signal transduction through interleukin-5 receptors." Cold Spring Harbor Synp.Quant.Biol.54. (1990)

[Publications] Sugamura,S.,et al.: "Analysis of mechanisms by which NK cells acquire increased cytotoxicity against class IMHC-eliminated targets." Cell.Immunol.119. 304-316 (1989)

[Publications] Fujii,M.,et al.: "Polyclonal activation of human lynphocytes streptococcal preparations.Evidence for interleukin2-independent generation“double negative(CD3 CD4 CD8 TcR16)"" J.Immunol.(1990)

[Publications] Shijubo,N.,et al.: "Functional analysis of mononuclear cells infiltration into tumors.A soluble factor involved in the regulation into tumors." J.Immunol.142. 2961-2967 (1989)

[Publications] Shijubo,N.,et al.: "Functional analysis of mononuclear cells infiltration into tumor-inflitration cells." Jpn.J.Cancer Res.81.

[Publications] Takeshita,T., et al.: "Monoclonal antibody defining a molecule possibly identical to the p75 submit of interleukin 2 receptor." The Journal of Experimental Medicine. 169. 1323-1332 (1989)

[Publications] Ohashi,Y.,et al.: "Differential expression of the interleukin 2 receptor subunits,p55 and p75 on various populations of primary peripheral blood mononuclear cells." The Journal of immunology. 143. 3548-3555 (1989)

[Publications] Sato,N.,et al.: "Anti-idiotype reactive with target molecule for mouse Lymphokine-activated killer cells." Cell.Immunol.121. 217-224 (1989)

[Publications] Nishimura,T.,et al.: "Inhibition of lymphokine-activated killer cell-mediated cytotoxicity by phorbol ester." The Journal of Immunology. 121. 2155-2161 (1989)

[Publications] Shimizu,J.,et al.: "Induction of tumor-specificin vivo protective immunization with tumor antigen-plused antigen-presenting cells." The Journal of immunology. 142. 1053-1059 (1989)

[Publications] Sano,S.,et al.: "Cytotoxic T lymphocyte unresponsiveness induced by prolonged treatment with immobilized anti-CD3:Association of impairment of cytolytic activity with temporary depletion of intracellular protein kinase." The Journal of immunology. 143. 2797-2805 (1989)

[Publications] Taga,T.,et al.: "Interleukin-6 triggers the association of its receptor with a possible signal transducer,gp130." Cell. 58. 573-581 (1989)

[Publications] Suematsu,S.,et al.: "IgG1 plasmacytosis in interleukin 6 transgenic mice." Proc.Nat1.Acad.Sci.USA.86. 7547-7551 (1989)

[Publications] Hirata,Y.,et al.: "Characterization of IL-6 receptor expression by monoclonal and polyclonal antibodies." The Journal of Immunology. 143. 2900-2906 (1989)

[Publications] Matsui,K.,et al.: "Us-and J-chain-mRNA expression are separately controlled event." The Journal of Immunology. 142. 2918-2923 (1989)

[Publications] Yoshimoto,T.,et al.: "IL-5 up-regulates but IL-4 down-regulates IL-2R expression on cloned B lymphoma line." The Journal of Immunology. 144. 183-190 (1990)

[Publications] Ohkawara,S.,et al.: "Interleukin 1 as an inflammatory hormon." Acta Pathol.Jap.39. 85-100 (1989)

[Publications] Goto,F.,et al.: "Biosynthesis of interleukin-1β at inflammatory site in rabbits.Kinetics and producing cells." Brit.J.Exp.Pathol.70. 597-606 (1989)

[Publications] Yamaguchi,N.,et al.: "Mechanisms of the interlekin 5-induced differentiation of B cells." J.Biochem.106. 837-843 (1989)

[Publications] Yamaguchi,N.,et al.: "Characterization of the murine interleukin 5 receptor by using a monoclonal antibody." Int.Immunol.2. 181-187 (1990)

高津聖志熊本大学, 医学部, 教授 (10107055)