Mechanistic basis for induction of T-cell anergy by PD-1, an immuno-regulatory receptor

• Project/Area Number: 19790356
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: 竹馬 俊介 Kyoto University, 医学研究科, 助教 (50437208)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: T細胞 / 免疫寛容 / 免疫制御 / 免疫学 / 自己免疫 / 抗原不応答性(アナジー) / がん免疫 / 免疫抑制 / ガン免疫

Research Abstract

ガンや、ウイルス感染においては、これと闘うTリンパ球が、初期活性化した後、徐々に無反応になることが問題となる。この不応答性が、活性化T細胞に発現するPD-1レセプターによって引き起こされること、PD-1が、活性化初期のIL-2産生を調節することによって、T細胞を不応答に陥れることを明らかにした。この研究によって、免疫反応の調節機構と、それに関連した難病の治療につながる知見が得られた。

Research Products

• [Journal Article] PD-1-mediated suppression of IL-2 production induces CD8+ T cell anergy in vivo (2009)
  • Author(s): Chikuma S, Terawaki S, Hayashi T, Nabeshima R, Yoshida T, Shibayama S, Okazaki T, Honjo T
  • Journal Title: J. Immunol. vol.182 Pages: 6682-6689
  • Peer Reviewed
• [Journal Article] Identification of QTLs that modify peripheral neuropathy in NOD. H2b-Pdcd1-/- mice (2009)
  • Author(s): Jiang F, Yoshida T, Nakaki F, Terawaki S, Chikuma S, Kato Y, Okazaki IM, Honjo T, Okazaki T
  • Journal Title: Int. Immunol. vol.21 Pages: 499-509
  • Peer Reviewed
• [Journal Article] The expression of differentiation markers in aquaporin deficient epidermis (2009)
  • Author(s): Hara-Chikuma M, Takahashi K, Chikuma S, Verkman AS, and Miyachi Y
  • Journal Title: Arch. Dermatol. Res. vol.301 Pages: 245-252
  • Peer Reviewed
• [Journal Article] PD-1-mediated suppression of IL-2 production induces CD8+T cell anergy in vivo (2009)
  • Author(s): Chikuma S., et.al.
  • Journal Title: The Journal of Immunology 182
  • Peer Reviewed
• [Journal Article] Identification of QTLs that modify peripheral neuropathy in NOD. H2b-Pdcd1-/- mice (2009)
  • Author(s): Jiang, Yoshida, Nakaki, Terawaki, Chikuma S, et.al.
  • Journal Title: International Immunology
  • Peer Reviewed
• [Journal Article] Expression of CTLA-4 and FoxP3 in cis protects from lethal lymphoproliferative disease (2007)
  • Author(s): Chikuma S, Bluestone J
  • Journal Title: Eur. J. Immunol. vol.37 Pages: 1285-1289
  • Peer Reviewed
• [Journal Article] Expression of CTLA-4 and FOXP3 in cis protects from lethal lymphoproliferative disease. (2007)
  • Author(s): Chikuma S and Bluestone JA
  • Journal Title: The European Journal of Immunology 37 Pages: 1285-1289
  • Peer Reviewed
• [Presentation] PD-1 induces T cellanergy by limiting autonomous IL-2 production (2008)
  • Author(s): Chikuma S., et.al.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-03
• [Presentation] マウスPD-1の転写機構/Transcriptional Mechanisms of Mouse PD-1 Gene (2008)
  • Author(s): Terawaki S, Chikuma S, et.al.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-03
• [Presentation] PD-1 induces T cell anergy by limiting autonomous IL-2 production (2008)
  • Author(s): Chikuma S, Terawaki S, Okazaki T, Honjo T
  • Organizer: 第38回日本免疫学会総会・学術集会, Vol.38, p.234
  • Place of Presentation: 京都
• [Presentation] Transcriptional mechanisms of mouse PD-1 gene (2008)
  • Author(s): Terawaki S, Chikuma S, Okazaki T, Honjo T
  • Organizer: 第38回日本免疫学会総会・学術集会, Vol.38, p.234
  • Place of Presentation: 京都