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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 | | Alloreactivity | | 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 http://creativecommons.org/licenses/by-nc-nd/4.0/ | | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/82147 |
| 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)
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Submitter: 武冨 紹信
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