Background: Biomarkers and immune-monitoring assays predicting operational tolerance in transplant recipients have not been established. Our aim was to develop an immune-monitoring assay to address tailoring immunosuppression (IS) of transplant recipients who can be weaned off IS. Methods: 2.5×10⁶ hu-PBMCs were injected intraperitoneally into NSG mice. Hu-PBMCs were obtained from humanized mice 21 days after reconstitution. The allo-reactivity by MLR and lymphocyte population were evaluated before and after reconstitution. Results: In healthy volunteers (n=5), the percentages of hu-CD3⁺ T cells were significantly increased after reconstitution (59.2±3.0 to 86.5±3.1%, mean±SEM, P<0.01). In particular, CD45RA^–CD62L^lo effector memory T cells were predominantly reconstituted (CD4⁺; 25.5±6.6 to 55.8±4.6%, P<0.05, CD8; 8.6±2.0 to 30.1±4.3 %, P<0.01). Consequently, the allo-reactivities (Stimulation index) were boosted after reconstitution (Fig.1a).The similar trends of both reconstituted cell populations and the allo-reactivities were observed in hu-PBMCs from living donor liver transplant recipients. Of note donor-hyporesponsiveness of hu-PBMCs from the recipients who achieved operational tolerance, were maintained after reconstitution (n=4, Fig.1b). Meanwhile the reactivities to donor and 3^rd party antigens of hu-PBMCs from the recipients treated with IS, differed after reconstitutionamong individuals (n=6, Fig.1b). As hu-PBMCs in humanized mice for 21 days possibly mimic the completely weaned off IS status, it is probable that the cases in whom donor-hyporesponsiveness retained after reconstitution being similar to operational tolerant cases, may wean off IS in clinical settings. Conclusion:A novel immune-monitoring assay exploring the capability of immune response to alloantigens without IS in humanized mice, may be used to identify recipients who have successfullyachieved operational tolerance.

CITATION INFORMATION: Fukasaku Y, Goto R, Ganchiku Y, Zaitsu M, Watanabe M, Kawamura N, Koshizuka Y, Yamashita K, Shimamura T, Taketomi A. Novel Personalized Immune-Monitoring Assay for Predicting Operational Tolerance by Using Humanized Mouse Model. Am J Transplant. 2017;17 (suppl 3).

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