Immunological accommodation, Treg/Breg and co-stimulatory signal in ABO-incompatible kidney transplantation

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09573
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Niigata University
• Principal Investigator: Saito Kazuhide 新潟大学, 医歯学系, 准教授 (20262438)
• Co-Investigator(Kenkyū-buntansha): 田崎 正行 新潟大学, 医歯学総合病院, 助教 (40571906)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ABO血液型不適合腎移植 / 免疫学的順応 / 共刺激分子

Outline of Final Research Achievements

We intended to confirm the role and of co-stimulatory signal in immunological accommodation induction in ABO-incompatible kidney transplantation. We extracted and cultured T/B cells from healthy volunteer and kidney transplant recipients. In healthy control, PD-1 and PD-L1 on CD3(+) T cells increased up to 57.27％,　39.31％, respectively, however PD-L2 was 0.68％. PD-1 and PD-L1 on CD19(+) B cell increased up to 10.60％ and 68.01％, respectively, and PD-L also increased to 7.9％.
On the other hand, in ABO-incompatible kidney transplant recipients who experienced graft rejection, PD-1, PD-L1 and PD-L2 on CD3(+) T cells increased up to 47.27％, 68.81％ and 53.22％, respectively, PD-1, PD-L1 and PD-L2 on CD19(+) B cells increased up to 20.20％, 48.64% and 15.9％, respectively.

Free Research Field

腎移植学

Academic Significance and Societal Importance of the Research Achievements

ABO血液型不適合腎移植においては術前脱感作療法を適切に行うことで抗体関連型拒絶反応を回避し、抗血液型抗体価が低値のまま安定し拒絶反応が起こらない免疫学的順応が誘導される。本研究では患者リンパ球培養系においてはTcell, B cellともにPD-1, PD-L1, PD-L2などの共刺激分子が健常対照に比して増加傾向にある可能性を示唆する結果が示された。機器故障により十分な検体数を持ってその確実性を証明することなく研究は終了せざるを得なかったが、ABO不適合移植の免疫学的順応に共刺激分子が関与している可能性を示唆する最初の結果であり今後の研究進展に資する可能性がある。