Requirement of TCR signal for the maintenance of gamma/delta T cells in peripheral tissue

• Project/Area Number: 26460572
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: Tani-ichi Shizue 京都大学, 医学研究科, 助教 (50432331)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: γδ T細胞 / TCR / ホメオスタシス / γδT細胞 / TCRシグナル / ガンマデルタT細胞

Outline of Final Research Achievements

Homeostasis of αβ T cells in peripheral tissue requires both TCR and IL-7 receptor signal. Although it is known that γδ T cells require IL-15 and IL-7 signal, it remains unknown whether γδ T cells require TCR signal for their homeostasis. Because the ligands for murine γδ TCR remain unclear, we tried to attenuate γδ TCR signal by down-regulating γδ TCR expression. To do this, we generated mice lacking one of the enhancers in the TCRγ locus. In this knockout mice, CD27+CD45RBhigh IFNγ-producing γδ T cell subsets in the peripheral lymphoid tissue were specifically reduced. Maintenance of this subset transferred to Rag2KO mice was impaired in enhancer knockout mice. These data suggest that at least CD27+CD45RBhigh IFNγ-producing γδ T cells require TCR signal for their homeostasis in peripheral tissue.

Research Products

• [Journal Article] STAT5 Orchestrates Local Epigenetic Changes for Chromatin Accessibility and Rearrangements by Direct Binding to the TCRγ Locus. (2015)
  • Author(s): Wagatsuma K, Tani-Ichi S, Liang B, Shitara S, Ishihara K, Abe M, Miyachi H, Kitano S, Hara T, Nanno M, Ishikawa H, Sakimura K, Nakao M, Kimura H, Ikuta K.
  • Journal Title: J Immunol. Volume: 195 Issue: 4 Pages: 1804-14
  • DOI: 10.4049/jimmunol.1302456
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Role of TCRgamma enhancer Egamma4 for the development and function of gamma delta T cells (2016)
  • Author(s): Shizue Tani-ichi and Koichi Ikuta
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: Melbourne, Australia
  • Int'l Joint Research
• [Presentation] 末梢組織でのガンマデルタT細胞維持におけるTCRシグナルの必要性 (2014)
  • Author(s): 谷一靖江、生田宏一
  • Organizer: 第24回 Kyoto T cell Conference
  • Place of Presentation: 京都平安ホテル
  • Year and Date: 2014-05-16 – 2014-05-17