Co-Inhibitors of Second Signal of Lymphocyte Response in Human Renal Transplants: PD-L2, GITR, and ILT-2/3/5 Positive Cells from Aspiration Biopsies Associate with Acute Rejection-Freedom  

作　　者：Paula D. P. Xavier José Gerardo G. Oliveira Paula D. P. Xavier;José Gerardo G. Oliveira(Instituto Português do Sangue e da Transplantação, área Transplantação, Rua do Bolama, Porto, Portugal;GCCT, Centro Hospitalar Universitário S. João, Alameda Hernani Monteiro, Porto, Portugal;CINTESIS, Faculdade de Medicina da Universidade do Porto, Alameda Hernani Monteiro, Porto, Portugal)

机构地区：[1]Instituto Português do Sangue e da Transplantaç ã o, área Transplantaç ã o, Rua do Bolama, Porto, Portugal [2]GCCT, Centro Hospitalar Universitário S. Joã o, Alameda Hernani Monteiro, Porto, Portugal [3]CINTESIS, Faculdade de Medicina da Universidade do Porto, Alameda Hernani Monteiro, Porto, Portugal

出　　处：《Open Journal of Nephrology》2021年第1期58-77,共20页肾脏病（英文）

摘　　要：<p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14</span><span> </span><span>-</span><span> </span><span>30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group </span><span>showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 </span><span>as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2</span><i><span>α</span></i><span>R and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significant</span><span>ly</span><span> positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR w</span><span>as</span><span> clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.</span> </p><p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14</span><span> </span><span>-</span><span> </span><span>30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group </span><span>showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 </span><span>as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2</span><i><span>α</span></i><span>R and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significant</span><span>ly</span><span> positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR w</span><span>as</span><span> clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.</span> </p>

关 键 词：Antigen-Presenting Cell Fine-Needle Aspiration Biopsy Glucocorticoid-Induced Tumor Necrosis Factor Receptor Immunoglobulin-Like Transcript Kidney Transplant Programmed Death-Ligand 2 

分 类 号：R73[医药卫生—肿瘤]