Elucidation of the molecular bases of the generation and maintenance of CTL memory by next generation DNA sequencer

• Project/Area Number: 22390095
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: The University of Tokyo
• Principal Investigator: MATSUSHIMA Kouji 東京大学, 大学院・医学系研究科, 教授 (50222427)
• Co-Investigator(Kenkyū-buntansha): HASHIMOTO Shinichi 金沢大学, 医学系, 特任教授 (00313099) ; KURACHI Makoto 東京大学, 大学院・医学系研究科, 助教 (00396722) ; UEHA Satoshi 東京大学, 大学院・医学系研究科, 助教 (00447385) ; ABE Jun 東京大学, 大学院・医学系研究科, 助教 (50581831)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2011: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2010: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
• Keywords: 遺伝子 / 感染症 / 免疫学 / 免疫記憶 / メモリーCTL / 老化

Research Abstract

Based on the gene expression analyses, we focused on thechemokine receptor CXCR3 and revealed that CXCR3 regulates the localization of CD8+ T cells within lymphoid tissues early after activation, which affects the formation of memoryCD8+ T cells. Memory CD8+ T cells up-regulated the expression of chemokine and cytokinegenes characteristic of CTLs, whereas down-regulated expression of ribosomal proteingenes associated with cell senescence. Furthermore, we found that 2nd memory up-regulated the NK cell specific genes as compared to 1st memory. Thus we would like to propose that these molecules might be a marker of senescent memory CTLs.

Research Products

• [Journal Article] Coordinated Changes in DNA Methylation in Antigen-Specific Memory CD4 T Cells (2013)
  • Author(s): Hashimoto S, Ogoshi K, Sasaki A, Abe J, Qu W, Nakatani Y, Ahsan B, Oshima K, Shand FH, Ametani A, Suzuki Y, Kaneko S, Wada T, Hattori M, Sugano S,Morishita S, Matsushima K
  • Journal Title: J Immunol Volume: 190 Issue: 8 Pages: 4076-4091
  • DOI: 10.4049/jimmunol.1202267
  • Peer Reviewed
• [Journal Article] Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin. (2012)
  • Author(s): Keisuke Nagao
  • Journal Title: Nature Immunology Volume: 13(8) Issue: 8 Pages: 744-752
  • DOI: 10.1038/ni.2353
  • Peer Reviewed
• [Journal Article] Genome-wide genetic variations are highly correlated with proximal DNA methylation patterns (2012)
  • Author(s): Qu W, Hashimoto S, Shimada A, Nakatani Y, Ichikawa K, Saito TL, Ogoshi K, Matsushima K, Suzuki Y, Sugano S, Takeda H, Morishita S.
  • Journal Title: Genome Res Volume: 22 Issue: 8 Pages: 1419-1425
  • DOI: 10.1101/gr.140236.112
  • Peer Reviewed
• [Journal Article] Chemokine receptor CXCR3 facilitates CD8(+) T cell differentiation into short-lived effector cells leading to memory degeneration (2011)
  • Author(s): Kurachi Makoto
  • Journal Title: The Journal of Experimental Medicine Volume: 208 Issue: 8 Pages: 1605-1620
  • DOI: 10.1084/jem.20102101
  • Peer Reviewed
• [Journal Article] Genome-wide profiling of DNA methylation in human cancer cells (2011)
  • Author(s): Katsumi Ogoshi, et al
  • Journal Title: Genomics Volume: 98 Issue: 4 Pages: 280-287
  • DOI: 10.1016/j.ygeno.2011.07.003
  • Peer Reviewed
• [Journal Article] A conceptual molecular network for chemotactic behaviors characterized by feedback of molecules cycling between the membrane and the cytos (2010)
  • Author(s): Otsuji M., et al
  • Journal Title: Science signaling Volume: 3
  • Peer Reviewed
• [Presentation] Bone marrow dysfunction and defective B lymphopoiesis during chronic GVHD (2012)
  • Author(s): 小杉瑞葉
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸国際展示場(兵庫)
  • Year and Date: 2012-12-05
• [Presentation] Destruction of hematopoietic niche after allogenic hematopoietic stem cell transplantation (2012)
  • Author(s): 小杉瑞葉
  • Organizer: 第34回日本炎症再生医学会
  • Place of Presentation: ホテル日航福岡(福岡)
  • Year and Date: 2012-07-05
• [Presentation] Destruction of hematopoietic niche after allogenic hematopoietic stem cell transplantation (2012)
  • Author(s): Mizuha Kosugi
  • Organizer: The 34th Annual Meeting on the Japanese Society of Inflammation and Regeneration
  • Place of Presentation: 福岡県（ホテル日航福岡）
  • Invited
• [Presentation] Bone marrow dysfunction and defective B lymphopoiesis during chronic GVHD (2012)
  • Author(s): Mizuha Kosugi
  • Organizer: The 41st Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: 兵庫県（神戸国際展示場）
• [Presentation] Chemokine receptor CXCR3 facilitates CD8+ T cell differentiation into short-lived effector cells leading to memory degeneration (2011)
  • Author(s): 倉知慎
  • Organizer: 米国免疫学会(AAI2011)
  • Place of Presentation: サンフランシスコ国際会議場(アメリカ合衆国)
  • Year and Date: 2011-05-16
• [Presentation] Chemokine receptor CXCR3 facilitates CD8^+ T cell differentiation into short-lived effector cells leading to memory degeneration (2011)
  • Author(s): 倉知慎
  • Organizer: 米国免疫学会(AAI2011)
  • Place of Presentation: サンフランシスコ国際会議場(アメリカ合衆国)
  • Year and Date: 2011-05-16
• [Presentation] Chemokine receptor CXCR3 facilitates CD8+T cell differentiation into short-lived effector cells leading to memory degeneration (2011)
  • Author(s): Makoto Kurachi
  • Organizer: Keystone Symposium
  • Place of Presentation: Fairmont Hotel (Banff, Canada)
  • Year and Date: 2011-02-08
• [Book] 改訂版分子予防環境医学生命科学研究の予防・環境医学への統合 (2010)
  • Author(s): 松島綱治
  • Total Pages: 850
  • Publisher: 本の泉社
• [Remarks]
  • URL: http://www.prevent.m.u-tokyo.ac.jp/
• [Remarks]
  • URL: http://www.prevent.m.u-tokyo.ac.jp/
• [Remarks]
  • URL: http://www.prevent.m.u-tokyo.ac.jp/