2003 Fiscal Year Annual Research Report

Th2細胞の分化・機能に関わる補助シグナル分子の解明

Research Project

Project/Area Number	14770144
Research Institution	Juntendo University
Principal Investigator	秋葉久弥順天堂大学, 医学部, 助手 (60338316)
Keywords	Th1 / Th2 / 補助シグナル分子 / OX40 / OX40L / ICOS / B7RP-1
Research Abstract	Th2細胞の分化・機能に関わる補助シグナル分子としてOX40/OX40L、ICOS/B7RP-1を候補に挙げ以下の研究結果を得た。生体内で起こるTh1/Th2細胞の分化誘導に及ぼすICOS/B7RP-1の機能解析を行うため、寄生虫Leishmania major (L. major)マウス感染系に抗B7RP-1モノクローナル抗体投与を行った。結果、L. major感染に対しTh1を誘導し抵抗性を示すC57BL/6マウスに効果が認められなかったのに対し、Th2を誘導し感染が増悪するBALB/cマウスにおいて明らかな症状の軽減が認められた。このマウスのリンパ節細胞をConA刺激した結果、IL-4,IL-5などのTh2サイトカインの産生が抑制された。またTh2サイトカインで誘導される血清IgE, IgG1量も有意に減少が認められた。これらの結果はICOS欠損マウスにおいても同様の結果が得られたことから、ICOS/B7RP-1は先に報告したOX40/OX40Lと同様に生体内においてTh2細胞の分化誘導に重要な役割をはたしている事が示唆された。マウスに羊赤血球やOVA-Alumなどを免疫して脾臓やリンパ節中に誘導されるCD4+ T細胞のOX40,ICOS, CXCR5(ケモカインレセプター)分子の発現パターンを解析した結果、活性化CD4+T細胞はICOS+ OX40- CXCR5+,ICOS+ OX40- CXCR5-,ICOS- OX40+ CXCR5-,ICOS+ OX40+ CXCR5-の4つのサブポピュレーションに分けられることが明らかとなった。このうちICOS+ OX40- CXCR5+ CD4+ T細胞は濾胞に移動して胚中心形成関わるヘルパーCD4+T細胞と考えられており、残る3つのポピュレーションの内いずれか、もしくは複数がTh2細胞へと分化するのではないかと考えている。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] Koichiro Matsumoto: "B7-DC regulates asthmatic response by an IFN-γ-dependent mechanism"The Journal of Immunology. 172(4). 2530-2541 (2004)
[Publications] Yasushi Miyahira: "A potent adjuvant effect of ligand to receptor activator of NF-κB gene for inducing antigen-specific CD8^+T cell response by DNA and viral vector vaccination"The Journal of Immunology. 171(12). 6344-6348 (2003)
[Publications] Yasushi Miyahira: "Involvement of ICOS-B7RP-1 costimulatory pathway in the regulation of immune responses to Leishmania major and Nippostrongylus brasiliensis infections"Immunology Letters. 89(2-3). 193-199 (2003)
[Publications] Takanori Kanai: "Blockade of B7-H1 suppresses the development of chronic intestinal inflammation"The Journal of Immunology. 171(8). 4156-4163 (2003)
[Publications] Fumihiko Tsushima: "Preferential contribution of B7-H1 to programmed death-1-mediated regulation of hapten-specific allergic inflammatory responses"European Journal of Immunology. 33(10). 2773-2782 (2003)
[Publications] Hideyuki Iwai: "Involvement of inducible costimulator-B7 homologous protein costimulatory pathway in murine lupus nephritis"The Journal of Immunology. 171(6). 2848-2854 (2003)
[Publications] Hiroshi Harada: "The role of the ICOS-B7h T cell costimulatory pathway in trnaplantation immunity"The Journal of Clinical Investigation. 122(2). 234-243 (2003)
[Publications] Shahram Salek-Ardakani: "OX40 (CD134) controls memory T helper 2 cells that drive ling inflammation"The Journal of Experimental Medicine. 198(2). 315-324 (2003)
[Publications] Alan D.Salama: "Critical role of the programmed death-1 (PD-1) pathway in regulation of experimental autoimmune encephalomyelitis"The Journal of Experimental Medicine. 198(1). 71-78 (2003)
[Publications] Mohammed Javeed I.Ansari: "The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice"The Journal of Experimental Medicine. 198(1). 63-69 (2003)
[Publications] Akihiko Hoshino: "Critical role for OX40 ligand in the development of pathogenic Th2 cells in a murine model of asthma"European Journal of Immunology. 33(4). 861-869 (2003)
[Publications] Teruji Totsuka: "Therapeutic effect of anti-OX40L and anti-TNF-α mabs in a murine model of chronic colitis"Am J Physiol Gastrointest Liver Physiol. 284(4). G595-G603 (2003)
[Publications] Xueli Yuan: "The role of the CD134-CD134 ligand costimulatory pathway in alloimmune responses in vivo"The Journal of Immunology. 170(6). 3741-3748 (2003)
[Publications] Bruce R.Blazar: "Ligation of OX40 (CD134) regulates graft-versus-host disease (GVHD) and graft rejection in allogenic bone marrow transplant recipients"Blood. 101(9). 3741-3748 (2003)

2003 Fiscal Year Annual Research Report

Th2細胞の分化・機能に関わる補助シグナル分子の解明

Principal Investigator

秋葉 久弥 順天堂大学, 医学部, 助手 (60338316)

Research Products

[Publications] Koichiro Matsumoto: "B7-DC regulates asthmatic response by an IFN-γ-dependent mechanism"The Journal of Immunology. 172(4). 2530-2541 (2004)

[Publications] Yasushi Miyahira: "A potent adjuvant effect of ligand to receptor activator of NF-κB gene for inducing antigen-specific CD8^+T cell response by DNA and viral vector vaccination"The Journal of Immunology. 171(12). 6344-6348 (2003)

[Publications] Yasushi Miyahira: "Involvement of ICOS-B7RP-1 costimulatory pathway in the regulation of immune responses to Leishmania major and Nippostrongylus brasiliensis infections"Immunology Letters. 89(2-3). 193-199 (2003)

[Publications] Takanori Kanai: "Blockade of B7-H1 suppresses the development of chronic intestinal inflammation"The Journal of Immunology. 171(8). 4156-4163 (2003)

[Publications] Fumihiko Tsushima: "Preferential contribution of B7-H1 to programmed death-1-mediated regulation of hapten-specific allergic inflammatory responses"European Journal of Immunology. 33(10). 2773-2782 (2003)

[Publications] Hideyuki Iwai: "Involvement of inducible costimulator-B7 homologous protein costimulatory pathway in murine lupus nephritis"The Journal of Immunology. 171(6). 2848-2854 (2003)

[Publications] Hiroshi Harada: "The role of the ICOS-B7h T cell costimulatory pathway in trnaplantation immunity"The Journal of Clinical Investigation. 122(2). 234-243 (2003)

[Publications] Shahram Salek-Ardakani: "OX40 (CD134) controls memory T helper 2 cells that drive ling inflammation"The Journal of Experimental Medicine. 198(2). 315-324 (2003)

[Publications] Alan D.Salama: "Critical role of the programmed death-1 (PD-1) pathway in regulation of experimental autoimmune encephalomyelitis"The Journal of Experimental Medicine. 198(1). 71-78 (2003)

[Publications] Mohammed Javeed I.Ansari: "The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice"The Journal of Experimental Medicine. 198(1). 63-69 (2003)

[Publications] Akihiko Hoshino: "Critical role for OX40 ligand in the development of pathogenic Th2 cells in a murine model of asthma"European Journal of Immunology. 33(4). 861-869 (2003)

[Publications] Teruji Totsuka: "Therapeutic effect of anti-OX40L and anti-TNF-α mabs in a murine model of chronic colitis"Am J Physiol Gastrointest Liver Physiol. 284(4). G595-G603 (2003)

[Publications] Xueli Yuan: "The role of the CD134-CD134 ligand costimulatory pathway in alloimmune responses in vivo"The Journal of Immunology. 170(6). 3741-3748 (2003)

[Publications] Bruce R.Blazar: "Ligation of OX40 (CD134) regulates graft-versus-host disease (GVHD) and graft rejection in allogenic bone marrow transplant recipients"Blood. 101(9). 3741-3748 (2003)

秋葉久弥順天堂大学, 医学部, 助手 (60338316)