Tolerance induction by CD8+/CD122+ Regulatory T Cells in Organ Transplantation

• Project/Area Number: 16H07121
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Nakamura Tsukasa 京都府立医科大学, 医学(系)研究科(研究院), 助教 (30777959)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 制御性T細胞 / 骨髄由来抑制細胞 / 臓器移植 / MDSCs / 免疫寛容

Outline of Final Research Achievements

Background: Myeloid-derived suppressor cells (MDSCs) maintain host immunity: regulating rejection. On the other hand, CD8+ Tregs also play a key role in preventing rejection. However, the relationship between MDSCs and CD8+ Tregs is unclear. Here, the results revealed that MDSCs have a potential to recruit CD8+/IL-10+ Tregs. Methods: MDSCs were isolated from bone-marrow culture with GM-CSF, M-CSF, and dexamethasone (MDSCs-Dex). In murine heterotopic cardiac transplantation, MDSCs were transferred through the tail vein. Results: Flow cytometric analyses showed that MDSCs-Dex led to significant recruitment of CD8+/IL-10+ Tregs (3.3±2.1% vs 10.2±3.6%, p<0.05). In a MDSCs transfer model, pathological findings also confirmed accumulation of CD8+/PD-1+ Tregs in an allograft. Conclusion:MDSCs might result in recruitment of CD8+/IL-10+ Tregs. These results suggested that the synergistic effect between MDSCs and CD8+ Tregs developed a tendency to immunological tolerance.

Research Products

• [Journal Article] Dexamethasone Prolongs Cardiac Allograft Survival in a Murine Model Through Myeloid-derived Suppressor Cells (2018)
  • Author(s): Nakao, T., Nakamura, T., Masuda, K., Matsuyama, T., Ushigome, H., Ashihara, E. et al.
  • Journal Title: Transplant Proceedings Volume: 50 Issue: 1 Pages: 299-304
  • DOI: 10.1016/j.transproceed.2017.11.014
  • Peer Reviewed
• [Presentation] Dexamethasone Prolongs Cardiac Allograft Survival in a Murine Model Through Myeloid-Derived Suppressor Cells. (2017)
  • Author(s): Nakao, T., Nakamura, T., Masuda, K., Mastuyama, T., Ashihara, E., Yoshimura, N.
  • Organizer: American Transplant Congress
  • Int'l Joint Research
• [Presentation] Aryl Hydrocarbon Receptor Regulates Myeloid Derived Suppressor Cells by Activating the ERK Signaling in a Murine Cardiac Transplantation Model. (2017)
  • Author(s): T. Nakamura, K. Masuda, N. Yoshimura.
  • Organizer: American Transplant Congress
  • Int'l Joint Research
• [Presentation] Aryl Hydrocarbon Receptor Regulates Myeloid Derived Suppressor Cells by Activating the ERK Signaling in a Murine Cardiac Transplantation Model (2017)
  • Author(s): Tsukasa Nakamura
  • Organizer: 2017 American Transplant Congress
  • Place of Presentation: McCormick Place - Lakeside Center, Chicago, IL, USA
  • Int'l Joint Research