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

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Title: Novel immunological approach to asses donor reactivity of transplant recipients using a humanized mouse model
Authors: Fukasaku, Yasutomo Browse this author
Goto, Ryoichi Browse this author →KAKEN DB
Ganchiku, Yoshikazu Browse this author
Emoto, Shin Browse this author
Zaitsu, Masaaki Browse this author →KAKEN DB
Watanabe, Masaaki Browse this author →KAKEN DB
Kawamura, Norio Browse this author →KAKEN DB
Fukai, Moto Browse this author →KAKEN DB
Shimamura, Tsuyoshi Browse this author →KAKEN DB
Taketomi, Akinobu Browse this author →KAKEN DB
Keywords: Liver transplantation
Humanized mouse
Issue Date: Jul-2020
Publisher: Elsevier
Journal Title: Human immunology
Volume: 81
Issue: 7
Start Page: 342
End Page: 353
Publisher DOI: 10.1016/j.humimm.2020.04.007
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 x 10(6) 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(-)CD62L(lo) T-EM 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 homeostatic proliferation of hu-T cells in the hu-PBMC-NSG mice. The immunological assay in humanized mice provides a new tool to assess recipient immunity in the absence of IS and explore the underlying mechanisms to maintaining operational tolerance.
Rights: © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 武冨 紹信

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