Low-dose IL-2 therapy to maintain Treg homeostasis under the use of calcineurin inhibitor

• Project/Area Number: 15K09504
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Okayama University
• Principal Investigator: Tanimoto Mitsune 岡山大学, 医歯薬学総合研究科, 特命教授 (10240805)
• Co-Investigator(Kenkyū-buntansha): 松岡 賢市 岡山大学, 医歯薬学総合研究科, 准教授 (90432640)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 造血幹細胞移植 / 制御性T細胞 / 移植片対宿主病 / 免疫寛容 / 同種造血幹細胞移植

Outline of Final Research Achievements

We performed allogeneic bone marrow transplantation from B6 donor into B6D2F1 recipient, and thereafter, we administrated immune suppressive agents including CsA,sirolimus and MMF. We found that CsA interfered Treg recovery while sirolimus and MMF promote Treg recovery. Moreover, we observed that low-dose IL-2 therapy and sirolimus syngeneically increased Treg population. Our findings suggest that the impact of LD-IL2 on Treg homeostasis after allogeneic SCT is mostly dependent on the kind of concomitant immune suppressive agents.

Research Products

• [Journal Article] PD-1 modulates regulatory T-cell homeostasis during low-dose interleukin-2 therapy. (2017)
  • Author(s): Asano T, Meguri Y, Yoshioka T, Kishi Y, Iwamoto M, Nakamura M, Sando Y, Yagita H, Koreth J, Kim HT, Alyea EP, Armand P, Cutler CS, Ho VT, Antin JH, Soiffer RJ, Maeda Y, Tanimoto M, Ritz J, Matsuoka KI.
  • Journal Title: Blood Volume: 129 Issue: 15 Pages: 2186-2197
  • DOI: 10.1182/blood-2016-09-741629
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and Overall Mortality. (2016)
  • Author(s): Fuji S, Inoue Y, Utsunomiya A, Moriuchi Y, Uchimaru K, Choi I, Otsuka E, Henzan H, Kato K, Tomoyose T, Yamamoto H, Kurosawa S, Matsuoka K, Yamaguchi T, Fukuda T.
  • Journal Title: J Clin Oncol Volume: 34(28) Issue: 28 Pages: 3426-33
  • DOI: 10.1200/jco.2016.67.8250
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Treatment of thrombotic microangiopathy after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin (2016)
  • Author(s): Fujiwara H, Maeda Y, Sando Y, Nakamura M, Tani K, Ishikawa T, Nishimori H, Matsuoka K, Fujii N, Kondo E, Tanimoto M.
  • Journal Title: Transfusion Volume: 56 Issue: 4 Pages: 886-92
  • DOI: 10.1111/trf.13437
  • Peer Reviewed
• [Journal Article] Vigorous inflammatory responses in noninfectious pulmonary complication induced by donor lymphocyte infusion. (2016)
  • Author(s): Nishie M, Fujii N, Mimura Y, Asano T, Mimura-Kimura Y, Aoe K, Aoe M, Nakashima H, Fujiwara H, Nishimori H, Matsuoka K, Kondo E, Maeda Y, Tanimoto M.
  • Journal Title: Transfusion Volume: 56 Issue: 1 Pages: 231-6
  • DOI: 10.1111/trf.13283
  • Peer Reviewed