Novel immunological approach to asses donor reactivity of transplant recipients using a humanized mouse model.

Novel immunological approach to asses donor reactivity of transplant recipients using a humanized mouse model. Hum Immunol. 2020 Apr 25;: Authors: Fukasaku Y, Goto R, Ganchiku Y, Emoto S, Zaitsu M, Watanabe M, Kawamura N, Fukai M, Shimamura T, Taketomi A Abstract In organ transplantation, a reproducible and robust immune-monitoring assay has not been established to determine individually tailored immunosuppressants (IS). We applied humanized mice reconstituted with human (hu-) peripheral blood mononuclear cells (PBMCs) obtained from living donor liver transplant recipients to evaluate their immune status. Engraftment of 2.5 × 106 hu-PBMCs from healthy volunteers and recipients in the NSG mice was achieved successfully. The reconstituted lymphocytes consisted mainly of hu-CD3+ lymphocytes with predominant CD45RA-CD62Llo TEM and CCR6-CXCR3+CD4+ Th1 cells in hu-PBMC-NSG mice. Interestingly, T cell allo-reactivity of hu-PBMC-NSG mice was amplified significantly compared with that of freshly isolated PBMCs (p < 0.05). Furthermore, magnified hu-T cell responses to donor antigens (Ag) were observed in 2/10 immunosuppressed recipients with multiple acute rejection (AR) experiences, suggesting that the immunological assay in hu-PBMC-NSG mice revealed hidden risks of allograft rejection by IS. Furthermore, donor Ag-specific hyporesponsiveness was maintained in recipients who had been completely weaned off IS (n = 4), despite homeosta...
Source: Human Immunology - Category: Allergy & Immunology Authors: Tags: Hum Immunol Source Type: research