Inhibition of CD4+ T cell function during infection with malaria parasite

• Project/Area Number: 21390125
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Parasitology (including Sanitary zoology)
• Research Institution: Nagasaki University
• Principal Investigator: YUI Katsuyuki 長崎大学, 大学院・医歯薬学総合研究科, 教授 (90274638)
• Co-Investigator(Kenkyū-buntansha): KIMURA Daisuke 長崎大学, 大学院・医歯薬学総合研究科, 助教 (50423637) ; MIZUSAKI Hirofumi 長崎大学, 大学院・医歯薬学総合研究科, 助教 (40467957)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2010: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2009: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: マラリア / 原虫 / T細胞 / 感染防御 / サイトカイン / 赤血球 / 感染 / 免疫抑制 / マウス / 感染モデル / インターロイキン2 / インターフェロンγ / 免疫

Research Abstract

We investigated mechanisms of the modulation of T cell immune responses during infection with Plasmodium berghei ANKA(PbA). CD4^+ T cells from PbA-infected mice inhibited IL-2 production of other CD4^+ T cells by cytokine-mediated mechanisms. The inhibitory cells were foxp3-activated CD4^+ T cells and were distinct from Tregs. The inhibitory cytokine produced by these CD4^+ T cells was not TGF-b or IL-10, and was identified as a novel T cell producing inhibitory cytokine X.

Research Products

• [Journal Article] DEN2 16681 strain utilizes specific glycochain of Syndecan-2 proteoglycan as a receptor (2012)
  • Author(s): Okamoto, K., Kinoshita, H., del Camen Parquet, M., Rawekiensya, M., Kimura, D., Yui, K., Alimul Islam, M., Hasebe, F., Morita, K.
  • Journal Title: J. Gen. Virol. Volume: 93 Pages: 761-770
• [Journal Article] Interferon regulatory factor-4 activates IL-2 and IL-4 promoters in cooperation with c-Rel (2011)
  • Author(s): Shindo, H., Yasui, K., Yamamoto, K., Honma, K., Yui, K., Kohno, K., Ma, Y. Chua, K. J., Kubo, Y., Aihara, H., Ito, T., Nagayasu, T., Matsuyama, T., Hayashi, H.
  • Journal Title: Cytokine Volume: 56(3) Pages: 564-572
  • NAID: 120006985203
• [Journal Article] Flt3 ligand prevents the development of cerebral malaria during infection with Plasmodium berghei ANKA (2011)
  • Author(s): Tamura, T., Kimura, K., Yuda, M., Yui, K.
  • Journal Title: Infection and Immunity Volume: 79(10) Pages: 3947-3956
• [Journal Article] Characterization of waves of leukocyte recruitment to the lung allograft and the effect of CTLA4-Ig (2011)
  • Author(s): Taguchi, T., Inamura, Y., Honma, K., Kimura, D., Miyakoda M., Miyazaki, T., Tsuchiya, T. Yamasaki, N., Tagawa, T., Nagayasu, T., Yui, K.
  • Journal Title: Acta Medica Nagasakientia Volume: 56 Pages: 27-34
  • NAID: 110008767588
• [Journal Article] Flt3 ligand prevents the development of cerebral malaria during infection with Plasmodium berghei ANKA (2011)
  • Author(s): T Tamura, K Kimura, M Yuda, K Yui
  • Journal Title: Infection and Immunity Volume: 79 Pages: 3947-3956
  • Peer Reviewed
• [Journal Article] Production of IFN-γby CD4+ T cells in response to malaria antigens is IL-2-dependent (2010)
  • Author(s): Kimura D., Miyakoda M., Honma K., Yuda M., Chinzei Y., and Yui K.
  • Journal Title: Int. Immunol. Volume: 22(12) Pages: 941-952
• [Journal Article] The JMJD3-IRF4 axis regulates M2 macrophage polarization and host response against helminth infection (2010)
  • Author(s): Satoh, T., Takeuchi, O., Vnadenbon, A., Yasuda, K., Tanaka, Y., Kumagai, Y., Miyake, T., Matsushita, K., Okazaki, T., Saitoh, T., Honma, K., Matsuyama, T., Yui, K., Tsujimura, T., Standley, D. M., Nakanishi, K., Nakai, K., Akira, S.
  • Journal Title: Nature Immunol. Volume: 11(10) Pages: 936-944
• [Journal Article] The JMJD3-IRF4 axis regulates M2 macrophage polarization and host response against helminth infection. (2010)
  • Author(s): Satoh, T., Takeuchi, O., Vnadenbon, A., Yasuda, K., Tanaka, Y., Kumagai, Y., Miyake, T., Matsushita, K., Okazaki, T., Saitoh, T., Honma, K., Matsuyama, T., Yui, K., Tsujimura, T., Standley, D.M., Nakanishi, K., Nakai, K., Akira, S.
  • Journal Title: Nature Immunology Volume: 11 Pages: 936-944
  • Peer Reviewed
• [Journal Article] Production of IFN-γ by CD4^+ T cells in response to malaria antigens is IL-2-dependent (2010)
  • Author(s): Kimura D., Miyakoda M., Honma K., Yuda M., Chinzei Y., Yui K.
  • Journal Title: International Immunology Volume: 22 Pages: 941-952
  • Peer Reviewed
• [Journal Article] マラリア感染防御とCD8^+ T細胞 (2010)
  • Author(s): 由井克之、都田真奈
  • Journal Title: 臨床免疫・アレルギー科 Volume: 55 Pages: 89-94
  • NAID: 40018704015
• [Presentation] マラリア赤内型および赤外型に対する獲得防御免疫の種特異性 (2012)
  • Author(s): 井上愛実、ズングラナ・オーグスチン、都田真奈、唐建霞、金子修、由井克之、カレントン・リチャード
  • Organizer: 第81回日本寄生虫学会大会
• [Presentation] マウスマラリア感染におけるFlt3 ligand発現による原虫血症抑制メカニズムの解析 (2012)
  • Author(s): 田村隆彦、木村一美、油田正夫、由井克之
  • Organizer: 第81回日本寄生虫学会大会
• [Presentation] マラリア原虫感染によって引き起こされるCD4^+ T細胞のIL-12産生抑制機序の解析 (2012)
  • Author(s): 木村大輔、都田真奈、本間季里、木村一美、原博満、吉田裕樹、由井克之
  • Organizer: 第81回日本寄生虫学会大会
• [Presentation] マラリア原虫感染によって誘導される制御性CD4+T細胞は液生因子によってIL-2産生を抑制する (2011)
  • Author(s): 木村大輔、都田真奈、本間季里、木村一美、由井克之
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-29
• [Presentation] モデル抗原組換えマラリア原虫を用いた肝細胞期防御免疫応答の解析 (2011)
  • Author(s): 木村一美、木村大輔、都田真奈、本間季里、田村隆彦、由井克之
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-27
• [Presentation] Flt3 ligand発現による実験的脳マラリア発症抑制メカニズムの解析 (2011)
  • Author(s): 田村隆彦、木村一美、油田正夫、由井克之
  • Organizer: 日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-18
• [Presentation] マラリア原虫感染における抗原特異的CD8+T細胞の分化 (2011)
  • Author(s): 都田真奈、木村大輔、本間季里、木村一美、油田正夫、由井克之
  • Organizer: 日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-18
• [Presentation] マラリア肝細胞期におけるCD8+とCD4+T細胞のエフェクター機構の解析 (2011)
  • Author(s): 木村一美、木村大輔、都田真奈、本間季里、田村隆彦、油田正夫、由井克之
  • Organizer: 日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-18
• [Presentation] マラリア原虫感染により誘導されるCD4+ T細胞はIL-2産生抑制の新規サイトカインを発現する (2011)
  • Author(s): 木村大輔、都田真奈、本間季里、木村一美、油田正夫、由井克之
  • Organizer: 日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-18
• [Presentation] Complete abrogation of sporozoite-induced sterile immunity by blood stage parasites of homologous and heterologous malaria species (2011)
  • Author(s): 井上愛実、Tang Jianxia、金子修、由井克之、Culleton Richard
  • Organizer: 日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-18
• [Presentation] Prevention of cerebral malaria by Flt3 ligand during infection with Plasmodium berghei ANKA (2011)
  • Author(s): T. Tamura, K. Kimura, M. Yuda, K. Yui
  • Organizer: 45^<th> annual Japan-US joint conference on parasitic diseases
• [Presentation] Flt3 ligand発現による実験的脳マラリア発症抑制メカニズムの解析 (2011)
  • Author(s): 田村隆彦、木村一美、油田正夫、由井克之
  • Organizer: 第80回日本寄生虫学会大会
• [Presentation] マラリア原虫感染における抗原特異的CD8+ T細胞の分化 (2011)
  • Author(s): 都田真奈、木村大輔、本間季里、木村一美、油田正夫、由井克之
  • Organizer: 第80回日本寄生虫学会大会
• [Presentation] モデル抗原組換えマラリア原虫を用いた肝細胞期防御免疫応答の解析 (2011)
  • Author(s): 木村一美、木村大輔、都田真奈、本間季里、田村隆彦、由井克之
  • Organizer: 第40回日本免疫学会学術集
• [Presentation] Regulation of IFN-γ production in CD4^+ T cells during infection with Plasmodium berghei (2010)
  • Author(s): 由井克之
  • Organizer: Adaptive and innate immune responses to neglected tropical diseases
  • Place of Presentation: San Diego(アメリカ合衆国)
  • Year and Date: 2010-01-11
• [Presentation] Regulation of INF-γProduction in CD4^+ T Cells during Infection with Plasmodium berghei (2010)
  • Author(s): K. Yui
  • Organizer: Adaptive and innate immune responses to neglected tropical diseases
  • Place of Presentation: San Diego, USA
• [Presentation] Production of IFN-γby CD4^+ T cells in response to malaria antigen is IL-2 dependent during infection with Plasmodium berghei (2010)
  • Author(s): D. Kimura, M. Miyakoda, K. Honma, K. Kimura, M. Yuda, Y. Chinzei, K. Yui
  • Organizer: Keystone Symposia on Molecular and cellular biology, Immunologic memory, Malaria : new approaches to understanding host-parasite interactions
  • Place of Presentation: Colorado, USA
• [Presentation] CD4^+ T細胞のマラリア原虫抗原特異的IFN-γ産生はIL-2依存的である (2010)
  • Author(s): 木村大輔、都田真奈、本間季里、木村一美、油田正夫、鎮西康雄、由井克之
  • Organizer: 2D-ML30第79回日本寄生虫学会大会
  • Place of Presentation: 旭川
• [Presentation] Production of IFN-γby CD4^+ T cells in response to malaria antigen is IL-2-dependent (2010)
  • Author(s): D. Kimura, M. Miyakoda, K. Honma, K. Kimura, M. Yuda, Y. Chinzei, K. Yui
  • Organizer: 14^<th> International congress of Immunology Kobe
• [Presentation] Reduction of the memory CD8^+ T cell responses during infection with Plasmodium berghei ANKA (2010)
  • Author(s): M. Miyakoda, D. Kimura, K. Honma, K. Kimura, M. Yuda, Y. Chinzei, K. Yui
  • Organizer: 14^<th> International congress of Immunology Kobe
• [Presentation] Complete abrogation of sporozoite-induced sterile immunity by blood stage parasites of homologous and heterologous malaria parasites (2010)
  • Author(s): M. Inoue, J. Tang, O. Kaneko, K. Yui, R.
  • Organizer: Culleton, Malaria J.
• [Presentation] Production of IFN-γ by CD4^+ T cells in response to malaria antigen is IL-2 dependent during infection with Plasmodium berghei (2010)
  • Author(s): D.Kimura, M.Miyakoda, K.Honma, K.Kimura, M.Yuda, Y.Chinzei, K.Yui
  • Organizer: Keystone Symposia
  • Place of Presentation: Colorado, USA
• [Presentation] CD4^+ T細胞のマラリア原虫抗原特異的IFN-γ産生はIL-2依存的である (2010)
  • Author(s): 木村大輔、都田真奈、本間季里、木村一美、油田正夫、鎮西康雄、由井克之
  • Organizer: 第79回日本寄生虫学会大会
  • Place of Presentation: 旭川
• [Presentation] Production of IFN-γ by CD4^+ T cells in response to malaria antigen is IL-2-dependent (2010)
  • Author(s): D.Kimura, M.Miyakoda, K.Honma, K.Kimura, M.Yuda, Y.Chinzei, K.Yui
  • Organizer: 14^<th> International congress of Immunology
  • Place of Presentation: 神戸
• [Presentation] IRF-4欠損CD4 T細胞においては、GATA-3発現だけではTh2分化に不十分である (2009)
  • Author(s): 本間季里、木村大輔、都田真奈、加山、松山俊文、由井克之
  • Organizer: 日本免疫学会学術集会(第39回)
  • Place of Presentation: 大阪市
  • Year and Date: 2009-12-03
• [Presentation] Induction and maintenance of memory CD8^+ T cells during infection with Plasmodium berghei ANKA (2009)
  • Author(s): 都田真奈、木村大輔、本間季里、田村隆彦、木村一美、由井克之
  • Organizer: 日本免疫学会学術集会(第39回)
  • Place of Presentation: 大阪市
  • Year and Date: 2009-12-02
• [Presentation] CD4^+ T cells from mice infected with Plasmodium berghei ANKA produce high levels of IFN-γ in response to cytokine like-molecule generated by other CD4^+ T cells (2009)
  • Author(s): 木村大輔、都田真奈、木村一美、田村隆彦、本間季里、由井克之
  • Organizer: 日本免疫学会学術集会(第39回)
  • Place of Presentation: 大阪市
  • Year and Date: 2009-12-02
• [Presentation] Antigen-specific T cell responses during infection with Plasmodium berghei : studies using OVA as a model malaria antigen (2009)
  • Author(s): 由井克之
  • Organizer: The 4^<th> Nagasaki Symposium on Tropical and Emerging Infectious Diseases
  • Place of Presentation: 長崎市
  • Year and Date: 2009-11-27
• [Remarks] ホームページ
  • URL: http://www.med.nagasaki-u.ac.jp/mmi/im/
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/mmi/im/
• [Remarks]
  • URL: http://www.med.nagasaki-u.ac.jp/mmi/im/
• [Patent(Industrial Property Rights)] 薬物送達複合体 (2010)
  • Inventor(s): 佐々木均、黒崎友亮、北原隆志、藤秀人、由井克之、平山謙二、森田公一
  • Industrial Property Rights Holder: 長崎大学
  • Industrial Property Number: 2010-043186
  • Filing Date: 2010-02-26