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Human PBMC-transferred murine MHC class I/II-deficient NOG mice enable long-term evaluation of human immune responses

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Cellular & Molecular Immunology 2018年第11期15卷 953-962页

作者： Tomonori Yaguchi Asuka Kobayashi Takashi Inozume Kenji Morii haruna nagumo Hiroshi Nishio Takashi Iwata Yuyo Ka Ikumi Katano Ryoji Ito Mamoru Ito Yutaka Kawakami Division of Cellular Signaling Institute for Advanced Medical ResearchKeio University School of MedicineTokyo 160-8582Japan Department of Dermatology Yamanashi University School of MedicineYamanashi 409-3898Japan Department of Obstetrics and Gynecology Keio University School of MedicineTokyo 160-8582Japan Central Institute for Experimental Animals Kanagawa 210-0821Japan

Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune ***,when human peripheral blood mononuclear cells(PBMCs)are transferred into NOG(NOD/Shi-scid,IL-2rg null)mice,severe graft versus host disease(GVHD)hinders long term detailed *** of human PBMCs into newly developed murine MHC class I-and class II-deficient NOG(NOG-dKO;NOG-Iab,B2m-double-knockout)mice showed sufficient engraftment of human immune cells with little sign of *** with influenza vaccine resulted in an increase in influenza-specific human IgG Ab,indicating induction of antigen-specific B cells in the NOG-dKO *** with human dendritic cells pulsed with HLA-A2 restricted cytomegalovirus peptide induced specific cytotoxic T cells,indicating the induction of antigen-specific T cells in the NOG-dKO *** cell therapies(ACTs)using melanoma antigen recognized by T cells(MART-1)-specific TCR-transduced activated T cells showed strong tumor growth inhibition in NOG-dKO mice without any sign of GVHD accompanied by preferential expansion of the transferred MART-1-specific T *** using cultured human melanoma infiltrating T cells also showed anti-tumor effects against autologous melanoma cells in NOG-dKO mice,in which changes in human cancer phenotypes by immune intervention,such as increased CD271 expression,could be ***,NOG-dKO mice are useful tools for more detailed analysis of both the induction and effector phases of T-cell and B-cell responses for a longer period than regular NOG mice.

关键词： adoptive cell therapy humanized mouse vaccine

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